Ramos-Jiménez J, Garduño-Torres B, Arias-Montaño JA

Idioma: Español
Referencias bibliográficas: 280
Paginas: 100-126
Archivo PDF: 513.67 Kb.

RESUMEN

Desde el reporte inicial por Dale y Laidlaw (1910) sobre el efecto de la histamina en la contracción del músculo liso intestinal y la vasodilatación, numerosas acciones adicionales han sido descritas. A nivel periférico, la histamina tiene efectos en la frecuencia y fuerza de la contracción cardiaca, la contracción del músculo liso de las vías respiratorias y del sistema gastrointestinal, las respuestas alérgica e inmune y la secreción gástrica ácida. En el Sistema Nervioso Central, la histamina regula funciones diversas como el ciclo sueño-vigilia, la conducta motora, la ingestión de agua y alimento, la conducta sexual, el aprendizaje y la memoria. Los efectos de la histamina se ejercen de manera primaria mediante la activación de receptores acoplados a proteínas G (metabotrópicos), de los cuales se han identificado cuatro subtipos (H1-H4). En este trabajo se revisan los mecanismos de síntesis y degradación de la histamina, las características farmacológicas y funcionales de los receptores metabotrópicos des critos, las funciones principales mediadas por estos receptores y las evidencias de la participación de la histamina en algunos procesos patológicos.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Dale HH, Laidlaw PP. The physiological action of beta-iminazolylethylamine. J Physiol 1910; 41:318- 44.

2. Parsons ME, Ganellin CR. Histamine and its receptors. Br J Pharmacol 2006; 147 (Suppl 1):S127-35.

3. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev 2008; 88:1183-241.

4. Ashford CA, Heller H, Smart GA. The action of histamine on hydrochloric acid and pepsin secretion in man. Br J Pharmacol Chemother 1949; 4:153-6.

5. Ash AS, Schild HO. Receptors mediating some actions of histamine. Br J Pharmacol Chemother 1966; 27:427-39.

6. Panula P, Yang HY, Costa E. Histamine-containing neurons in the rat hypothalamus. Proc Natl Acad Sci U S A 1984; 81:2572-6.

7. Watanabe T, Taguchi Y, Shiosaka S, Tanaka J, Kubota H, Terano Y, et al. Distribution of the histaminergic neuron system in the central nervous system of rats; a fluorescent immunohistochemical analysis with histidine decarboxylase as a marker. Brain Res 1984; 295:13-25.

8. Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 2008; 7:41-53.

9. Haas H, Panula P. The role of histamine and the tuberomamillary nucleus in the nervous system. Nat Rev Neurosci 2003; 4:121-30.

10. Masini E, Di Bello MG, Raspanti S, Fomusi Ndisang J, Baronti R, Cappugi P, et al. The role of histamine in platelet aggregation by physiological and immunological stimuli. Inflamm Res 1998; 47:211-20.

11. Zwadlo-Klarwasser G, Vogts M, Hamann W, Belke K, Baron J, Schmutzler W. Generation and subcellular distribution of histamine in human blood monocytes and monocyte subsets. Inflamm Res 1998; 47:434-9.

12. Kubo Y, Nakano K. Regulation of histamine synthesis in mouse CD4+ and CD8+ T lymphocytes. Inflamm Res 1999; 48:149-53.

13. Coruzzi G, Morini G, Adami M, Grandi D. Role of histamine H3 receptors in the regulation of gastric functions. J Physiol Pharmacol 2001; 52:539-53.

14. Garbarg M, Barbin G, Bischoff S, Pollard H, Schwartz JC. Dual localization of histamine in an ascending neuronal pathway and in non-neuronal cells evidenced by lesions in the lateral hypothalamic area. Brain Res 1976; 106:333-48.

15. Wada H, Inagaki N, Itowi N, Yamatodani A. Histaminergic neuron system: morphological features and possible functions. Agents Actions (Suppl) 1991; 33:11-27.

16. Palacios JM, Mengod G, Grau M, Picatoste F, Blanco I. Pyridoxal-5’-phosphate as a cofactor for rat brain histidine decarboxylase. J Neurochem 1978; 30:213-6.

17. Schwartz JC, Arrang JM, Garbarg M, Pollard H, Ruat M. Histaminergic transmission in the mammalian brain. Physiol Rev 1991; 71:1-51.

18. Schwartz JC, Lampart C, Rose C. Histamine formation in rat brain in vivo: effects of histidine loads. J Neurochem 1972; 19:801-10.

19. Prell GD, Hough LB, Khandelwal J, Green JP. Lack of a precursor-product relationship between histamine and its metabolites in brain after histidine loading. J Neurochem 1996; 67:1938-44.

20. Tran VT, Snyder SH. Histidine decarboxylase. Purification from fetal rat liver, immunologic properties, and histochemical localization in brain and stomach. J Biol Chem 1981; 256:680-6.

21. Martin SA, Bishop JO. Purification and characterization of histidine decarboxylase from mouse kidney. Biochem J 1986; 234:349-54.

22. Savany A, Cronenberger L. Isolation and properties of multiple forms of histidine decarboxylase from rat gastric mucosa. Biochem J 1982; 205:405-12.

23. Takamatsu S, Nakashima I, Nakano K. Modulation of endotoxin-induced histamine synthesis by cytokines in mouse bone marrow-derived macrophages. J Immunol 1996; 156:778-85.

24. Tanaka S, Deai K, Konomi A, Takahashi K, Yamane H, Sugimoto Y, et al. Expression of L-histidine decarboxylase in granules of elicited mouse polymorphonuclear leukocytes. Eur J Immunol 2004; 34:1472-82.

25. Panula P, Lintunen M, Karlstedt K. Histamine in brain development and tumors. Semin Cancer Biol 2000; 10:11-4.

26. Sieja K, Stanosz S, von Mach-Szczypinski J, Olewniczak S, Stanosz M. Concentration of histamine in serum and tissues of the primary ductal breast cancers in women. Breast 2005; 14:236-41.

27. Bolton E, King J, Morris DL. H2-antagonists in the treatment of colon and breast cancer. Semin Cancer Biol 2000; 10:3-10.

28. Hernandez-Angeles A, Soria-Jasso LE, Ortega A, Arias-Montano JA. Histamine H1 receptor activation stimulates mitogenesis in human astrocytoma U373 MG cells. J Neurooncol 2001; 55:81-9.

29. Hegyesi H, Somlai B, Varga VL, Toth G, Kovacs P, Molnar EL, et al. Suppression of melanoma cell proliferation by histidine decarboxylase specific antisense oligonucleotides. J Invest Dermatol 2001; 117:151-3.

30. Lefranc F, Yeaton P, Brotchi J, Kiss R. Cimetidine, an unexpected anti-tumor agent, and its potential for the treatment of glioblastoma. Int J Oncol 2006; 28:1021-30.

31. Stephan V, Kuhr J, Urbanek R. Anti-IgE- and complement-induced histamine release from peripheral leukocytes in normals and atopics. Int Arch Allergy Appl Immunol 1989; 90:326-30.

32. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev 1997; 77:1033-79.

33. Tung RS, Lichtenstein LM. Cyclic AMP agonist inhibition increases at low levels of histamine release from human basophils. J Pharmacol Exp Ther 1981; 218:642-6.

34. Alfonso A, Cabado AG, Vieytes MR, Botana LM. Functional compartments in rat mast cells for cAMP and calcium on histamine release. Cell Signal 2000; 12:343-50.

35. Verdiere M, Rose C, Schwartz JC. Synthesis and release of histamine studied on slices from rat hypothalamus. Eur J Pharmacol 1975; 34:157-68.

36. Van der Werf JF, Bast A, Bijloo GJ, Van der Vliet A, Timmerman H. HA autoreceptor assay with superfused slices of rat brain cortex and electrical stimulation. Eur J Pharmacol 1987; 138:199-206.

37. Arrang JM, Garbarg M, Schwartz JC. Auto-inhibi- tion of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 1983; 302:832-7.

38. Reinheimer T, Baumgartner D, Hohle KD, Racke K, Wessler I. Acetylcholine via muscarinic receptors inhibits histamine release from human isolated bronchi. Am J Respir Crit Care Med 1997; 156:389-95.

39. Reinheimer T, Mohlig T, Zimmermann S, Hohle KD, Wessler I. Muscarinic control of histamine release from airways. Inhibitory M1-receptors in human bronchi but absence in rat trachea. Am J Respir Crit Care Med 2000; 162:534-8.

40. Gulat-Marnay C, Lafitte A, Arrang JM, Schwartz JC. Modulation of histamine release and synthesis in the brain mediated by α2-adrenoceptors. J Neurochem 1989; 53:513-8.

41. Okakura-Mochizuki K, Mochizuki T, Yamamoto Y, Horii A, Yamatodani A. Endogenous GABA modulates histamine release from the anterior hypothalamus of the rat. J Neurochem 1996; 67:171-6.

42. Wollin A. Histamine uptake and its methylation by isolated oxyntic cells. Clin Invest Med 1987; 10:136-9.

43. Loiselle J, Wollin A. Mucosal histamine elimination and its effect on acid secretion in rabbit gastric mucosa. Gastroenterology 1993; 104:1013-20.

44. Haddock RC, Mack P, Leal S, Baenziger NL. The histamine degradative uptake pathway in human vascular endothelial cells and skin fibroblasts is dependent on extracellular Na+ and Cl. J Biol Chem 1990; 265:14395-401.

45. Sakurai E, Oreland L, Nishiyama S, Kato M, Watanabe T, Yanai K. Evidence for the presence of histamine uptake into the synaptosomes of rat brain. Pharmacology 2006; 78:72-80.

46. Huszti Z. Carrier-mediated high affinity uptake system for histamine in astroglial and cerebral endothelial cells. J Neurosci Res 1998; 51:551-8.

47. Osredkar D, Burnik-Papler T, Pecavar B, Kralj-Iglic V, Krzan M. Kinetic and pharmacological properties of [3H]-histamine transport into cultured type 1 astrocytes from neonatal rats. Inflamm Res 2009; 58:94-102.

48. Schayer RW. Catabolism of physiological quantities of histamine in vivo. Physiol Rev 1959; 39:116-26.

49. Ogasawara M, Yamauchi K, Satoh Y, Yamaji R, Inui K, Jonker JW, et al. Recent advances in molecular pharmacology of the histamine systems: organic cation transporters as a histamine transporter and histamine metabolism. J Pharmacol Sci 2006; 101:24-30.

50. Reilly MA, Schayer RW. In vivo studies on histamine catabolism and its inhibition. Br J Pharmacol 1970; 38:478-89.

51. Burkard WP, Gey KF, Pletscher A. Diamine oxidase in the brain of vertebrates. J Neurochem 1963; 10:183-6.

52. Gengs C, Leung HT, Skingsley DR, Iovchev MI, Yin Z, Semenov EP, et al. The target of Drosophila photoreceptor synaptic transmission is a histamine-gated chloride channel encoded by ort (hclA). J Biol Chem 2002; 277:42113-20.

53. Hardie RC. A histamine-activated chloride channel involved in neurotransmission at a photoreceptor synapse. Nature 1989; 339:704-6.

54. Roeder T. Metabotropic histamine receptors--nothing for invertebrates? Eur J Pharmacol 2003; 466:85-90.

55. Hatton GI, Yang QZ. Ionotropic histamine receptors and H2 receptors modulate supraoptic oxytocin neuronal excitability and dye coupling. J Neurosci 2001; 21:2974-82.

56. Hill SJ, Ganellin CR, Timmerman H, Schwartz JC,Shankley NP, Young JM, et al. International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev 1997; 49:253-78.

57. Faucard R, Schwartz JC. Neuropharmacology of histamine in brain. In: Sibley DR, Hanin I, Kuhar M, Skolnick P, eds. Handbook of Contemporary Neuropharmacology: John Wiley & Sons, Inc.; 2007:299-363.

58. Hill SJ. Distribution, properties, and functional characteristics of three classes of histamine receptors. Pharmacol Rev 1990; 42:45-83.

59. Arrang JM, Drutel G, Garbarg M, Ruat M, Traiffort E, Schwartz JC. Molecular and functional diversity of histamine receptor subtypes. Ann N Y Acad Sci 1995; 757:314-23.

60. Martinez-Mir MI, Pollard H, Moreau J, Arrang JM, Ruat M, Traiffort E, et al. Three histamine receptors (H1, H2 and H3) visualized in the brain of human and non-human primates. Brain Res 1990; 526:322-7.

61. Yanai K, Watanabe T, Yokoyama H, Hatazawa J, Iwata R, Ishiwata K, et al. Mapping of histamine H1 receptors in the human brain using [11C]pyrilamine and positron emission tomography. J Neurochem 1992; 59:128-36.

62. Fujimoto K, Horio Y, Sugama K, Ito S, Liu YQ, Fukui H. Genomic cloning of the rat histamine H1 receptor. Biochem Biophys Res Commun 1993; 190:294-301.

63. Horio Y, Mori Y, Higuchi I, Fujimoto K, Ito S, Fukui H. Molecular cloning of the guinea-pig histamine H1 receptor gene. J Biochem 1993; 114:408-14.

64. Inoue I, Taniuchi I, Kitamura D, Jenkins NA, Gilbert DJ, Copeland NG, et al. Characteristics of the mouse genomic histamine H1 receptor gene. Genomics 1996; 36:178-81.

65. De Backer MD, Gommeren W, Moereels H, Nobels G, Van Gompel P, Leysen JE, et al. Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor. Biochem Ramos-Jiménez et al. Biophys Res Commun 1993; 197:1601-8.

66. Ruat M, Schwartz JC. Photoaffinity labeling and electrophoretic identification of the H1-receptor: comparison of several brain regions and animal species. J Neurochem 1989; 53:335-9.

67. Fukui H, Fujimoto K, Mizuguchi H, Sakamoto K,Horio Y, Takai S, et al. Molecular cloning of the human histamine H1 receptor gene. Biochem Biophys Res Commun 1994; 201:894-901.

68. Donaldson J, Hill SJ. Histamine-induced hydrolysis of polyphosphoinositides in guinea-pig ileum and brain. Eur J Pharmacol 1986; 124:255-65.

69. Esbenshade TA, Kang CH, Krueger KM, Miller TR, Witte DG, Roch JM, et al. Differential activation of dual signaling responses by human H1 and H2 histamine receptors. J Recept Signal Transduct Res 2003; 23:17-31.

70. Zerbes M, Bunn SJ, Powis DA. Histamine causes Ca2+ entry via both a store-operated and a store-independent pathway in bovine adrenal chromaffin cells. Cell Calcium 1998; 23:379-86.

71. Hough LB. Genomics meets histamine receptors: new subtypes, new receptors. Mol Pharmacol 2001; 59:415-9.

72. Lantoine F, Iouzalen L, Devynck MA, Millanvoye- Van Brussel E, David-Dufilho M. Nitric oxide production in human endothelial cells stimulated by histamine requires Ca2+ influx. Biochem J 1998; 330 ( Pt 2):695-9.

73. Li H, Burkhardt C, Heinrich UR, Brausch I, Xia N, Forstermann U. Histamine upregulates gene expression of endothelial nitric oxide synthase in human vascular endothelial cells. Circulation 2003; 107:2348-54.

74. Richelson E. Histamine H1 receptor-mediated guanosine 3’,5’-monophosphate formation by cultured mouse neuroblastoma cells. Science 1978; 201:69-71.

75. Smith BN, Armstrong WE. The ionic dependence of the histamine-induced depolarization of vasopressin neurones in the rat supraoptic nucleus. J Physiol 1996; 495 ( Pt 2):465-78.

76. Weiger T, Stevens DR, Wunder L, Haas HL. HistamineH1 receptors in C6 glial cells are coupled to calcium-dependent potassium channels via release of calcium from internal stores. Naunyn Schmiedebergs Arch Pharmacol 1997; 355:559-65.

77. Selbach O, Brown RE, Haas HL. Long-term increase of hippocampal excitability by histamine and cyclic AMP. Neuropharmacology 1997; 36:1539-48.

78. Leurs R, Traiffort E, Arrang JM, Tardivel-Lacombe J, Ruat M, Schwartz JC. Guinea pig histamine H1 receptor. II. Stable expression in Chinese hamster ovary cells reveals the interaction with three major signal transduction pathways. J Neurochem 1994; 62:519-27.

79. Garbarg M, Schwartz JC. Synergism between histamine H1- and H2-receptors in the cAMP response in guinea pig brain slices: effects of phorbol esters and calcium. Mol Pharmacol 1988; 33:38-43.

80. Hill SJ, Young JM, Marrian DH. Specific binding of 3H-mepyramine to histamine H1 receptors in intestinal smooth muscle. Nature 1977; 270:361-3.0

81. Bouthenet ML, Ruat M, Sales N, Garbarg M, Schwartz JC. A detailed mapping of histamine H1- receptors in guinea-pig central nervous system established by autoradiography with [125I]iodobolpyramine. Neuroscience 1988; 26:553-600.

82. Bakker RA, Nicholas MW, Smith TT, Burstein ES, Hacksell U, Timmerman H, et al. In vitro pharmacology of clinically used central nervous system-active drugs as inverse H1 receptor agonists. J Pharmacol Exp Ther 2007; 322:172-9.

83. Simons FE. Advances in H1-antihistamines. N Engl J Med 2004; 351:2203-17.

84. Black JW, Duncan WA, Durant CJ, Ganellin CR, Parsons EM. Definition and antagonism of histamine H2 -receptors. Nature 1972; 236:385-90.

85. Traiffort E, Pollard H, Moreau J, Ruat M, Schwartz JC, Martinez-Mir MI, et al. Pharmacological characterization and autoradiographic localization of histamine H2 receptors in human brain identified with [125I] iodoaminopotentidine. J Neurochem 1992; 59:290-9.

86. Gantz I, Schaffer M, DelValle J, Logsdon C, Campbell V, Uhler M, et al. Molecular cloning of a gene encoding the histamine H2 receptor. Proc Natl Acad Sci U S A 1991; 88:429-33.

87. Gantz I, Munzert G, Tashiro T, Schaffer M, Wang L, DelValle J, et al. Molecular cloning of the human histamine H2 receptor. Biochem Biophys Res Commun 1991; 178:1386-92.

88. Ruat M, Traiffort E, Arrang JM, Leurs R, Schwartz JC. Cloning and tissue expression of a rat histamine H2-receptor gene. Biochem Biophys Res Commun 1991; 179:1470-8.

89. Traiffort E, Vizuete ML, Tardivel-Lacombe J, Souil E, Schwartz JC, Ruat M. The guinea pig histamine H2 receptor: gene cloning, tissue expression and chromosomal localization of its human counterpart. Biochem Biophys Res Commun 1995; 211:570-7.

90. Montminy MR, Gonzalez GA, Yamamoto KK. Regulation of cAMP-inducible genes by CREB. Trends Neurosci 1990; 13:184-8.

91. Montminy M. Transcriptional regulation by cyclic AMP. Annu Rev Biochem 1997; 66:807-22.

92. Delvalle J, Tsunoda Y, Williams JA, Yamada T. Regulation of [Ca2+]i by secretagogue stimulation of canine gastric parietal cells. Am J Physiol 1992; 262:G420-6.

93. Traiffort E, Ruat M, Arrang JM, Leurs R, Piomelli D, Schwartz JC. Expression of a cloned rat histamine H2 receptor mediating inhibition of arachidonate release and activation of cAMP accumulation. Proc Natl Acad Sci U S A 1992; 89:2649-53.

94. Wellner-Kienitz MC, Bender K, Meyer T, Pott L. Coupling to Gs and Gq/11 of histamine H2 receptors heterologously expressed in adult rat atrial myocytes. Biochim Biophys Acta 2003; 1642:67-77.

95. Gajtkowski GA, Norris DB, Rising TJ, Wood TP. Specific binding of 3H-tiotidine to histamine H2 receptors in guinea pig cerebral cortex. Nature 1983; 304:65-7.

96. Ruat M, Traiffort E, Bouthenet ML, Schwartz JC,Hirschfeld J, Buschauer A, et al. Reversible and irreversible labeling and autoradiographic localization of the cerebral histamine H2 receptor using [125I]iodinated probes. Proc Natl Acad Sci U S A 1990; 87:1658-62.

97. Leurs R, Smit MJ, Timmerman H. Molecular pharmacological aspects of histamine receptors. Pharmacol Ther 1995; 66:413-63.

98. Alexander SP, Mathie A, Peters JA. Guide to Receptors and Channels (GRAC), 3rd edition. Br J Pharmacol 2008; 153 (Suppl 2):S1-209.

99. Leurs R, Bakker RA, Timmerman H, de Esch IJ. The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov 2005; 4:107-20.

100. Imamura M, Seyedi N, Lander HM, Levi R. Functional identification of histamine H3-receptors in the human heart. Circ Res 1995; 77:206-10.

101. Wada H, Inagaki N, Itowi N, Yamatodani A. Histaminergic neuron system in the brain: distribution and possible functions. Brain Res Bull 1991; 27:367-70.

102. Pollard H, Moreau J, Arrang JM, Schwartz JC. A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas. Neuroscience 1993; 52:169-89.

103. Drutel G, Peitsaro N, Karlstedt K, Wieland K, Smit MJ, Timmerman H, et al. Identification of rat H3 receptor isoforms with different brain expression and signaling properties. Mol Pharmacol 2001; 59:1-8.

104. Pillot C, Heron A, Cochois V, Tardivel-Lacombe J, Ligneau X, Schwartz JC, et al. A detailed mapping of the histamine H3 receptor and its gene transcripts in rat brain. Neuroscience 2002; 114:173-93.

105. Lovenberg TW, Roland BL, Wilson SJ, Jiang X, Pyati J, Huvar A, et al. Cloning and functional expression of the human histamine H3 receptor. Mol Pharmacol 1999; 55:1101-7.

106. Leurs R, Hoffmann M, Wieland K, Timmerman H. H3 receptor gene is cloned at last. Trends Pharmacol

107. Morisset S, Sasse A, Gbahou F, Heron A, Ligneau X, Tardivel-Lacombe J, et al. The rat H3 receptor: gene organization and multiple isoforms. Biochem Biophys Res Commun 2001; 280:75-80.

108. Tardivel-Lacombe J, Rouleau A, Heron A, Morisset S, Pillot C, Cochois V, et al. Cloning and cerebral expression of the guinea pig histamine H3 receptor: evidence for two isoforms. Neuroreport 2000; 11:755-9.

109. Rouleau A, Heron A, Cochois V, Pillot C, Schwartz JC, Arrang JM. Cloning and expression of the mouse histamine H3 receptor: evidence for multiple isoforms. J Neurochem 2004; 90:1331-8.

110. Strakhova MI, Fox GB, Carr TL, Witte DG, Vortherms TA, Manelli AM, et al. Cloning and characterization of the monkey histamine H3 receptor isoforms. Eur J Pharmacol 2008; 601:8-15.

111. Tardivel-Lacombe J, Morisset S, Gbahou F, Schwartz JC, Arrang JM. Chromosomal mapping and organization of the human histamine H3 receptor gene. Neuroreport 2001; 12:321-4.

112. Coge F, Guenin SP, Audinot V, Renouard-Try A, Beauverger P, Macia C, et al. Genomic organization and characterization of splice variants of the human histamine H3 receptor. Biochem J 2001; 355:279-88.

113. Wellendorph P, Goodman MW, Burstein ES, Nash NR, Brann MR, Weiner DM. Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H3 receptor. Neuropharmacology 2002; 42:929-40.

114. Bongers G, Bakker RA, Leurs R. Molecular aspects of the histamine H3 receptor. Biochem Pharmacol 2007; 73:1195-204.

115. Clark MA, Korte A, Egan RW. Guanine nucleotides and pertussis toxin reduce the affinity of histamine H3 receptors on AtT-20 cells. Agents Actions 1993; 40:129-34.

116. Molina-Hernandez A, Nunez A, Sierra JJ, Arias- Montano JA. Histamine H3 receptor activation inhibits107. Morisset S, Sasse A, Gbahou F, Heron A, Ligneau X, Tardivel-Lacombe J, et al. The rat H3 receptor: gene organization and multiple isoforms. Biochem Biophys Res Commun 2001; 280:75-80.

117. Silver RB, Poonwasi KS, Seyedi N, Wilson SJ,Lovenberg TW, Levi R. Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings. Proc Natl Acad Sci U S A 2002; 99:501-6.

118. Rouleau A, Ligneau X, Tardivel-Lacombe J, Morisset S, Gbahou F, Schwartz JC, et al. Histamine H3-receptor-mediated [35S]GTP gamma[S] binding: evidence for constitutive activity of the recombinant and native rat and human H3 receptors. Br J Pharmacol 2002; 135:383-92.

119. Silver RB, Mackins CJ, Smith NC, Koritchneva IL, Lefkowitz K, Lovenberg TW, et al. Coupling of histamine H3 receptors to neuronal Na+/H+ exchange: a novel protective mechanism in myocardial ischemia. Proc Natl Acad Sci U S A 2001; 98:2855-9.

120. Oike M, Kitamura K, Kuriyama H. Histamine H3- receptor activation augments voltage-dependent Ca2+ current via GTP hydrolysis in rabbit saphenous artery. J Physiol 1992; 448:133-52.

121. Bongers G, Sallmen T, Passani MB, Mariottini C,Wendelin D, Lozada A, et al. The Akt/GSK-3beta axis as a new signaling pathway of the histamine H3 receptor. J Neurochem 2007; 103:248-58.

122. Morisset S, Rouleau A, Ligneau X, Gbahou F, Tardivel-Lacombe J, Stark H, et al. High constitutive activity of native H3 receptors regulates histamine neurons in brain. Nature 2000; 408:860-4.

123. Wieland K, Bongers G, Yamamoto Y, Hashimoto T, Yamatodani A, Menge WM, et al. Constitutive activity of histamine H3 receptors stably expressed in SK-N-MC cells: display of agonism and inverse agonism by H3 antagonists. J Pharmacol Exp Ther 2001; 299:908-14.

124. Arrang JM, Garbarg M, Lancelot JC, Lecomte JM, Pollard H, Robba M, et al. Highly potent and selective ligands for histamine H3-receptors. Nature 1987; 327:117-23.

125. Ligneau X, Garbarg M, Vizuete ML, Diaz J, Purand K, Stark H, et al. [125I]iodoproxyfan, a new antagonist to label and visualize cerebral histamine H3 receptors. J Pharmacol Exp Ther 1994; 271:452-9.

126. Hew RW, Hodgkinson CR, Hill SJ. Characterization of histamine H3-receptors in guinea-pig ileum with H3- selective ligands. Br J Pharmacol 1990; 101:621-4.

127. Menkveld GJ, Timmerman H. Inhibition of electrically evoked contractions of guinea-pig ileum preparations mediated by the histamine H3 receptor. Eur J Pharmacol 1990; 186:343-7.

128. Kathmann M, Schlicker E, Detzner M, Timmerman H. Nordimaprit, homodimaprit, clobenpropit and imetit: affinities for H3 binding sites and potencies in a functional H3 receptor model. Naunyn Schmiedebergs Arch Pharmacol 1993; 348:498-503.

129. Nakamura T, Itadani H, Hidaka Y, Ohta M, Tanaka K. Molecular cloning and characterization of a new human histamine receptor, HH4R. Biochem Biophys Res Commun 2000; 279:615-20.

130. Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S. Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. J Biol Chem 2000; 275:36781-6.

131. Liu C, Ma X, Jiang X, Wilson SJ, Hofstra CL, Blevitt J, et al. Cloning and pharmacological characterization of a fourth histamine receptor (H4) expressed in bone marrow. Mol Pharmacol 2001; 59:420-6.

132. Morse KL, Behan J, Laz TM, West RE, Jr., Greenfeder SA, Anthes JC, et al. Cloning and characterization of a novel human histamine receptor. J Pharmacol Exp Ther 2001; 296:1058-66.

133. Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, et al. Discovery of a novel member of the histamine receptor family. Mol Pharmacol 2001; 59:427-33.

134. Zhu Y, Michalovich D, Wu H, Tan KB, Dytko GM, Mannan IJ, et al. Cloning, expression, and pharmacological characterization of a novel human histamine receptor. Mol Pharmacol 2001; 59:434-41.

135. O’Reilly M, Alpert R, Jenkinson S, Gladue RP, Foo S, Trim S, et al. Identification of a histamine H4 receptor on human eosinophils--role in eosinophil chemotaxis. J Recept Signal Transduct Res 2002; 22:431-48.

136. Coge F, Guenin SP, Rique H, Boutin JA, Galizzi JP. Structure and expression of the human histamine H4- receptor gene. Biochem Biophys Res Commun 2001; 284:301-9.

137. Dunford PJ, O’Donnell N, Riley JP, Williams KN, Karlsson L, Thurmond RL. The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells. J Immunol 2006; 176:7062-70.

138. Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP. Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther 2003; 305:1212-21.

139. Buckland KF, Williams TJ, Conroy DM. Histamine induces cytoskeletal changes in human eosinophils via the H4 receptor. Br J Pharmacol 2003; 140:1117-27.

140. Liu C, Wilson SJ, Kuei C, Lovenberg TW. Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species ariation. J Pharmacol Exp Ther 2001; 299:121-30.

141. Jablonowski JA, Grice CA, Chai W, Dvorak CA, Venable JD, Kwok AK, et al. The first potentand selective non-imidazole human histamine H4 receptor antagonists. J Med Chem 2003; 46:3957-60.

142. Terzioglu N, van Rijn RM, Bakker RA, De Esch IJ, Leurs R. Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H4 receptor antagonists. Bioorg Med Chem Lett 2004; 14:5251-6.

143. Venable JD, Cai H, Chai W, Dvorak CA, Grice CA, Jablonowski JA, et al. Preparation and biological evaluation of indole, benzimidazole, and thienopyrrole piperazine carboxamides: potent human histamine H4 antagonists. J Med Chem 2005; 48:8289-98.

144. Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung WP, Hofstra CL, Jiang W, et al. A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther 2004; 309:404-13.

145. Varga C, Horvath K, Berko A, Thurmond RL, Dunford PJ, Whittle BJ. Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat. Eur J Pharmacol 2005; 522:130-8.

146. Dunford PJ, Williams KN, Desai PJ, Karlsson L, McQueen D, Thurmond RL. Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J Allergy Clin Immunol 2007; 119:176-83.0

147. Bell JK, McQueen DS, Rees JL. Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice. Br J Pharmacol 2004; 142:374-80.

148. Ling P, Ngo K, Nguyen S, Thurmond RL, Edwards JP, Karlsson L, et al. Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 2004; 142:161-71.

149. Smits RA, Lim HD, Stegink B, Bakker RA, de Esch IJ, Leurs R. Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. J Med Chem 2006; 49:4512-6.

150. Hashimoto T, Harusawa S, Araki L, Zuiderveld OP, Smit MJ, Imazu T, et al. A selective human H4- receptor agonist: (-)-2-cyano-1-methyl-3-[(2R,5R)-5- [1H-imidazol-4(5)-yl]tetrahydrofuran-2-y] methylguanidine. J Med Chem 2003; 46:3162-5.

151. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R. Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther 2005; 314:1310-21.

152. Akdis CA, Simons FE. Histamine receptors are hot in immunopharmacology. Eur J Pharmacol 2006; 533:69-76.

153. Kotlikoff MI, Murray RK, Reynolds EE. Histamineinduced calcium release and phorbol antagonism in cultured airway smooth muscle cells. Am J Physiol 1987; 253:C561-6.

154. Knight DA, Stewart GA, Thompson PJ. Histamineinduced contraction of human isolated bronchus is enhanced by endogenous prostaglandin F2α and activation of TP receptors. Eur J Pharmacol 1997; 319:261-7.

155. Gardner TW, Lesher T, Khin S, Vu C, Barber AJ, Brennan WA, Jr. Histamine reduces ZO-1 tightjunction protein expression in cultured retinal microvascular endothelial cells. Biochem J 1996; 320 ( Pt 3):717-21.

156. Tiruppathi C, Minshall RD, Paria BC, Vogel SM, Malik AB. Role of Ca2+ signaling in the regulation of endothelial permeability. Vascul Pharmacol 2002; 39:173-85.

157. Guo ZG, Levi R, Graver LM, Robertson DA,Gay WA, Jr. Inotropic effects of histamine in human myocardium: differentiation between positive and negative components. J Cardiovasc Pharmacol 1984; 6:1210-5.

158. Noble EP, Bommer M, Liebisch D, Herz A. H1-histaminergic activation of catecholamine release by chromaffin cells. Biochem Pharmacol 1988; 37:221-8.

159. Holzer P. Neurogenic vasodilatation and plasma leakage in the skin. Gen Pharmacol 1998; 30:5-11.

160. Marshall I. Characterization and distribution of histamine H1- and H2-receptors in precapillary vessels. J Cardiovasc Pharmacol 1984; 6 (Suppl 4):S587-97.

161. Stander S, Steinhoff M. Pathophysiology of pruritus in atopic dermatitis: an overview. Exp Dermatol 2002; 11:12-24.

162. Lovell P, Vender RB. Management and treatment of pruritus. Skin Therapy Lett 2007; 12:1-6.

163. Furutani K, Aihara T, Nakamura E, Tanaka S, Ichikawa A, Ohtsu H, et al. Crucial role of histamine for regulation of gastric acid secretion ascertained by histidine decarboxylase-knockout mice. J Pharmacol Exp Ther 2003; 307:331-8.

164. Chen D, Aihara T, Zhao CM, Hakanson R, Okabe S. Differentiation of the gastric mucosa. I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes. Am J Physiol Gastrointest Liver Physiol 2006; 291:G539-44.

165. Tanaka S, Konomi A, Takahashi K, Ichikawa A. Histamine synthesis in mouse polymorphonuclear neutrophils. Inflamm Res 2002; 51 (Suppl 1):S17-8.

166. Kobayashi T, Tonai S, Ishihara Y, Koga R, Okabe S, Watanabe T. Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor- deficient mice. J Clin Invest 2000; 105:1741-9.

167. Monge L, Garcia-Villalon AL, Fernandez N, Garcia JL, Gomez B, Dieguez G. In vitro relaxation of dog cerebral veins in response to histamine is mediated by histamine H2 receptors. Eur J Pharmacol 1997; 338:135-41.

168. Schubert ML, Peura DA. Control of gastric acid secretion in health and disease. Gastroenterology 2008; 134:1842-60.

169. Brimblecombe RW, Duncan WA, Durant GJ, Ganellin CR, Parsons ME, Black JW. The pharmacology of cimetidine, a new histamine H2-receptor antagonist. Br J Pharmacol 1975; 53:435P-6P.

170. Dembinski A, Warzecha Z, Ceranowicz P, Brzozo-wski T, Dembinski M, Konturek SJ, et al. Role of capsaicin-sensitive nerves and histamine H1, H2, and H3 receptors in the gastroprotective effect of histamine against stress ulcers in rats. Eur J Pharmacol 2005; 508:211-21.

171. Trzeciakowski JP. Inhibition of guinea pig ileum contractions mediated by a class of histamine receptor resembling the H3 subtype. J Pharmacol Exp Ther 1987; 243:874-80.

172. Ichinose M, Barnes PJ. Inhibitory histamine H3- receptors on cholinergic nerves in human airways. Eur J Pharmacol 1989; 163:383-6.

173. Obuchowicz R, Pawlik MW, Brzozowski T, Konturek SJ, Pawlik WW. Involvement of central and peripheral histamine H3 receptors in the control of the vascular tone and oxygen uptake in the mesenteric circulation of the rat. J Physiol Pharmacol 2004; 55:255-67.

174. Zhang M, Thurmond RL, Dunford PJ. The histamine H4 receptor: a novel modulator of inflammatory and immune disorders. Pharmacol Ther 2007; 113:594-606.

175. Tanaka S, Ichikawa A. Recent advances in molecular pharmacology of the histamine systems: immune regulatory roles of histamine produced by leukocytes. J Pharmacol Sci 2006; 101:19-23.

176. Pincus SH, DiNapoli AM, Schooley WR. Superoxide production by eosinophils: activation by histamine. J Invest Dermatol 1982; 79:53-7.

177. Anwar AR, Kay AB. H1-receptor dependence of histamine-induced enhancement of human eosinophil C3b rosettes. Clin Exp Immunol 1980; 42:196-9.

178. Nakane H, Sonobe Y, Watanabe T, Nakano K. Histamine: its novel role as an endogenous regulator of Con A-dependent T cell proliferation. Inflamm Res 2004; 53:324-8.

179. Banu Y, Watanabe T. Augmentation of antigen receptor-mediated responses by histamine H1 receptor signaling. J Exp Med 1999; 189:673-82.

180. Jutel M, Klunker S, Akdis M, Malolepszy J, Thomet OA, Zak-Nejmark T, et al. Histamine upregulates Th1 and downregulates Th2 responses due to different patterns of surface histamine 1 and 2 receptor expression. Int Arch Allergy Immunol 2001; 124:190-2.

181. Kubes P, Kanwar S. Histamine induces leukocyte rolling in post-capillary venules. A P-selectin-mediated event. J Immunol 1994; 152:3570-7.

182. Lo WW, Fan TP. Histamine stimulates inositol phosphate accumulation via the H1-receptor in cultured human endothelial cells. Biochem Biophys Res Commun 1987; 148:47-53.

183. Yamaki K, Thorlacius H, Xie X, Lindbom L, Hedqvist P, Raud J. Characteristics of histamineinduced leukocyte rolling in the undisturbed microcirculation of the rat mesentery. Br J Pharmacol 1998; 123:390-9.

184. Kleine-Tebbe J, Buschauer A, Friese A, Schunack W, Kunkel G. Modulation of IgE-mediated histamine release from human leukocytes by a new class of histamine H2-agonists. Agents Actions 1992; 35:185-91.

185. Seligmann BE, Fletcher MP, Gallin JI. Histamine modulation of human neutrophil oxidative metabolism, locomotion, degranulation, and membrane potential changes. J Immunol 1983; 130:1902-9.

186. Jutel M, Watanabe T, Klunker S, Akdis M, Thomet OA, Malolepszy J, et al. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 2001; 413:420-5.

187. Idzko M, la Sala A, Ferrari D, Panther E, Herouy Y, Dichmann S, et al. Expression and function of histamine receptors in human monocyte-derived dendritic cells. J Allergy Clin Immunol 2002; 109:839-46.

188. Elenkov IJ, Webster E, Papanicolaou DA, Fleisher TA, Chrousos GP, Wilder RL. Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors. J Immunol 1998; 161:2586-93.

189. Sansoni P, Silverman ED, Khan MM, Melmon KL, Engleman EG. Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells. J Clin Invest 1985; 75:650-6.

190. Fujimoto M, Kimata H. Histamine inhibits immunoglobulin production via histamine H2 receptors without affecting cell growth in human B cells. Clin Immunol Immunopathol 1994; 73:96-102.

191. Bissonnette EY. Histamine inhibits tumor necrosis factor alpha release by mast cells through H2 and H3 receptors. Am J Respir Cell Mol Biol 1996; 14:620-6.

192. Gutzmer R, Diestel C, Mommert S, Kother B, Stark H, Wittmann M, et al. Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. J Immunol 2005; 174:5224-32.

193. Fokkens WJ, Godthelp T, Holm AF, Blom H, Mulder PG, Vroom TM, et al. Dynamics of mast cells in the nasal mucosa of patients with allergic rhinitis and non-allergic controls: a biopsy study. Clin Exp Allergy 1992; 22:701-10.

194. Slater A, Smallman LA, Drake-Lee AB. Increase in epithelial mast cell numbers in the nasal mucosa of patients with perennial allergic rhinitis. J Laryngol Otol 1996; 110:929-33.

195. Godot V, Arock M, Garcia G, Capel F, Flys C, Dy M, et al. H4 histamine receptor mediates optimal migration of mast cell precursors to CXCL12. J Allergy Clin Immunol 2007; 120:827-34.

196. Gantner F, Sakai K, Tusche MW, Cruikshank WW,Center DM, Bacon KB. Histamine H4 and H2 receptors control histamine-induced interleukin-16 release from human CD8(+) T cells. J Pharmacol Exp Ther 2002; 303:300-7.

197. Airaksinen MS, Alanen S, Szabat E, Visser TJ, Panula P. Multiple neurotransmitters in the tuberomammillary nucleus: comparison of rat, mouse, and guinea pig. J Comp Neurol 1992; 323:103-16.

198. Brown RE, Stevens DR, Haas HL. The physiology of brain histamine. Prog Neurobiol 2001; 63:637-72.

199. Kanayama H, Yasuhara O, Matsuo A, Tooyama I, Aimi Y, Bellier JP, et al. Expression of a splice variant of choline acetyltransferase in magnocellular neurons of the tuberomammillary nucleus of rat. Neuroscience 2003; 118:243-51.

200. Takeshita Y, Watanabe T, Sakata T, Munakata M, Ishibashi H, Akaike N. Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus. Neuroscience 1998; 87:797-805.

201. Brown RE, Haas HL. On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus. J Physiol 1999; 515 ( Pt 3):777-86.

202. Garcia M, Floran B, Arias-Montano JA, Young JM, Aceves J. Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata. Neuroscience 1997; 80:241-9.

203. Arias-Montano JA, Floran B, Garcia M, Aceves J, Young JM. Histamine H3 receptor-mediated inhibition of depolarization-induced, dopamine D1 receptor-dependent release of [3H]-gamma-aminobutryic acid from rat striatal slices. Br J Pharmacol 2001; 133:165-71.

204. Arias-Montano JA, Floran B, Floran L, Aceves J, Young JM. Dopamine D1 receptor facilitation of depolarization-induced release of gamma-aminobutyric acid in rat striatum is mediated by the cAMP/ PKA pathway and involves P/Q-type calcium channels. Synapse 2007; 61:310-9.

205. Schlicker E, Werthwein S, Zentner J. Histamine H3 receptor-mediated inhibition of noradrenaline release in the human brain. Fundam Clin Pharmacol 1999; 13:120-2.

206. Schlicker E, Fink K, Hinterthaner M, Gothert M. Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors. Naunyn Schmiedebergs Arch Pharmacol 1989; 340:633-8.

207. Schlicker E, Behling A, Lummen G, Gothert M. Histamine H3A receptor-mediated inhibition of noradrenaline release in the mouse brain cortex. Naunyn Schmiedebergs Arch Pharmacol 1992; 345:489-93.

208. Schlicker E, Fink K, Detzner M, Gothert M. Histamine inhibits dopamine release in the mouse striatum via presynaptic H3 receptors. J Neural Transm Gen Sect 1993; 93:1-10.

209. Blandina P, Giorgetti M, Cecchi M, Leurs R, Timmerman H, Giovannini MG. Histamine H3 receptor inhibition of K+-evoked release of acetylcholine from rat cortex in vivo. Inflamm Res 1996; 45 (Suppl 1):S54-5.

210. Prast H, Tran MH, Fischer H, Kraus M, Lamberti C, Grass K, et al. Histaminergic neurons modulate acetylcholine release in the ventral striatum: role of H3 histamine receptors. Naunyn Schmiedebergs Arch Pharmacol 1999; 360:558-64.

211. Fink K, Schlicker E, Neise A, Gothert M. Involvement of presynaptic H3 receptors in the inhibitory effect of histamine on serotonin release in the rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol 1990; 342:513-9.

212. Threlfell S, Cragg SJ, Kallo I, Turi GF, Coen CW, Greenfield SA. Histamine H3 receptors inhibit serotonin release in substantia nigra pars reticulata. J Neurosci 2004; 24:8704-10.

213. Molina-Hernandez A, Nuñez A, Arias-Montano JA. Histamine H3-receptor activation inhibits dopamine synthesis in rat striatum. Neuroreport 2000; 11:163-6.

214. Lin JS, Sakai K, Vanni-Mercier G, Jouvet M. A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats. Brain Res 1989; 479:225-40.

215. Vanni-Mercier G, Gigout S, Debilly G, Lin JS. Waking selective neurons in the posterior hypothalamus and their response to histamine H3-receptor ligands: an electrophysiological study in freely moving cats. Behav Brain Res 2003; 144:227-41.

216. Chu M, Huang ZL, Qu WM, Eguchi N, Yao MH, Urade Y. Extracellular histamine level in the frontal cortex is positively correlated with the amount of wakefulness in rats. Neurosci Res 2004; 49:417-20.

217. Huang ZL, Mochizuki T, Qu WM, Hong ZY, Watanabe T, Urade Y, et al. Altered sleep-wake characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout mice. Proc Natl Acad Sci U S A 2006; 103:4687-92.

218. Barbier AJ, Bradbury MJ. Histaminergic control of sleep-wake cycles: recent therapeutic advances for sleep and wake disorders. CNS Neurol Disord Drug Targets 2007; 6:31-43.

219. Parmentier R, Anaclet C, Guhennec C, Brousseau E, Bricout D, Giboulot T, et al. The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders. Biochem Pharmacol 2007; 73:1157-71.

220. Lin JS, Sakai K, Vanni-Mercier G, Arrang JM,Garbarg M, Schwartz JC, et al. Involvement of histaminergic neurons in arousal mechanisms demonstrated with H3-receptor ligands in the cat. Brain Res 1990; 523:325-30.

221. Huang ZL, Qu WM, Li WD, Mochizuki T, Eguchi N, Watanabe T, et al. Arousal effect of orexin A depends on activation of the histaminergic system. Proc Natl Acad Sci U S A 2001; 98:9965-70.

222. Parmentier R, Ohtsu H, Djebbara-Hannas Z, Valatx JL, Watanabe T, Lin JS. Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control.J Neurosci 2002; 22:7695-711.

223. Nelson LE, Guo TZ, Lu J, Saper CB, Franks NP,Maze M. The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway. Nat Neurosci 2002; 5:979-84.

224. Hong ZY, Huang ZL, Qu WM, Eguchi N, Urade Y, Hayaishi O. An adenosine A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats. J Neurochem 2005; 92:1542-9.

225. Lin JS, Sakai K, Jouvet M. Hypothalamo-preoptic histaminergic projections in sleep-wake control in the cat. Eur J Neurosci 1994; 6:618-25.

226. McCormick DA, Bal T. Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci 1997; 20:185-215.

227. McCormick DA. Neurotransmitter actions in the thalamus and cerebral cortex. J Clin Neurophysiol 1992; 9:212-23.

228. Wada H, Inagaki N, Yamatodani A, Watanabe T. Is the histaminergic neuron system a regulatory center for whole-brain activity? Trends Neurosci 1991; 14:415-8.

229. Doi T, Sakata T, Yoshimatsu H, Machidori H, Kurokawa M, Jayasekara LA, et al. Hypothalamic neuronal histamine regulates feeding circadian rhythm in rats. Brain Res 1994; 641:311-8.

230. Sakata T, Yoshimatsu H, Kurokawa M. Hypothalamic neuronal histamine: implications of its homeostatic control of energy metabolism. Nutrition 1997; 13:403-11.

231. Sakata T, Yoshimatsu H, Kurokawa M. Thermoregulation modulated by hypothalamic histamine in rats. Inflamm Res 1997; 46 (Suppl 1):S35-6.

232. Ookuma K, Sakata T, Fukagawa K, Yoshimatsu H, Kurokawa M, Machidori H, et al. Neuronal histamine in the hypothalamus suppresses food intake in rats. Brain Res 1993; 628:235-42.

233. Yoshimatsu H, Chiba S, Tajima D, Akehi Y, Sakata T. Histidine suppresses food intake through its conversion into neuronal histamine. Exp Biol Med (Maywood) 2002; 227:63-8.

234. Malmlof K, Zaragoza F, Golozoubova V, Refsgaard HH, Cremers T, Raun K, et al. Influence of a selective histamine H3 receptor antagonist on hypothalamic neural activity, food intake and body weight. Int J Obes (Lond) 2005; 29:1402-12.

235. Fukagawa K, Sakata T, Shiraishi T, Yoshimatsu H, Fujimoto K, Ookuma K, et al. Neuronal histamine modulates feeding behavior through H1-receptor in rat hypothalamus. Am J Physiol 1989; 256:R605-11.

236. Morimoto T, Yamamoto Y, Yamatodani A. Leptin facilitates histamine release from the hypothalamus in rats. Brain Res 2000; 868:367-9.

237. Morimoto T, Yamamoto Y, Mobarakeh JI, Yanai K, Watanabe T, Yamatodani A. Involvement of the histaminergic system in leptin-induced suppression of food intake. Physiol Behav 1999; 67:679-83.

238. Takahashi K, Suwa H, Ishikawa T, Kotani H. Targeted disruption of H3 receptors results in changes in brain histamine tone leading to an obese phenotype. J Clin Invest 2002; 110:1791-9.

239. Tokita S, Takahashi K, Kotani H. Recent advances in molecular pharmacology of the histamine systems: physiology and pharmacology of histamine H3 receptor: roles in feeding regulation and therapeutic potential for metabolic disorders. J Pharmacol Sci 2006; 101:12-8.

240. Leibowitz SF. Histamine: a stimulatory effect on drinking behavior in the rat. Brain Res 1973; 63:440-4.

241. Lecklin A, Etu-Seppala P, Stark H, Tuomisto L. Effects of intracerebroventricularly infused histamine and selective H1, H2 and H3 agonists on food and water intake and urine flow in Wistar rats. Brain Res 1998; 793:279-88.

242. Knigge U, Willems E, Kjaer A, Jorgensen H, Warberg J. Histaminergic and catecholaminergic interactions in the central regulation of vasopressin and oxytocin secretion. Endocrinology 1999; 140:3713-9.

243. Magrani J, de Castro ESE, Athanazio R, Improta L, Fregoneze JB. Involvement of central H1 and H2 receptors in water intake induced by hyperosmolarity, hypovolemia and central cholinergic stimulation. Physiol Behav 2006; 89:241-9.

244. Clark WG, Lipton JM. Changes in body temperature after administration of acetylcholine, histamine, morphine, prostaglandins and related agents: II. Neurosci Biobehav Rev 1985; 9:479-552.

245. Chen Z, Sugimoto Y, Kamei C. Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature in mice. Methods Find Exp Clin Pharmacol 1995; 17:669-75.

246. Poulakos JJ, Gertner SB. Studies on the cardiovascular actions of central histamine H1 and H2 receptors. J Pharmacol Exp Ther 1989; 250:500-7.

247. Kjaer A, Knigge U, Plotsky PM, Bach FW, Warberg J. Histamine H1 and H2 receptor activation stimulates ACTH and β-endorphin secretion by increasing corticotropin- releasing hormone in the hypophyseal portal blood. Neuroendocrinology 1992; 56:851-5.

248. Miyake A, Ohtsuka S, Nishizaki T, Tasaka K, Aono T, Tanizawa O, et al. Involvement of H1 histamine receptor in basal and estrogen-stimulated luteinizing hormone-releasing hormone secretion in rats in vitro. Neuroendocrinology 1987; 45:191-6.

249. Knigge U, Matzen S, Warberg J. Histaminergic stimulation of prolactin secretion mediated via H1- or H2-receptors: dependence on routes of administration. Neuroendocrinology 1986; 44:41-8.

250. Netti C, Guidobono F, Olgiati VR, Sibilia V, Pagani F, Pecile A. Influence of brain histaminergic system on episodic growth hormone secretion in the rat. Neuroendocrinology 1982; 35:43-7.

251. Mitsuma T, Nogimori T, Sun DH, Chaya M. Effects of histamine and related compounds on thyrotropin secretion in rats. Horm Res 1986; 23:99-105.

252. Onodera K, Yamatodani A, Watanabe T, Wada H. Neuropharmacology of the histaminergic neuron system in the brain and its relationship with behavioral disorders. Prog Neurobiol 1994; 42:685-702.

253. Bristow LJ, Bennett GW. Biphasic effects of intraaccumbens histamine administration on spontaneous motor activity in the rat; a role for central histamine receptors. Br J Pharmacol 1988; 95:1292-302.

254. Chiavegatto S, Nasello AG, Bernardi MM. Histamine and spontaneous motor activity: biphasic changes, receptors involved and participation of the striatal dopamine system. Life Sci 1998; 62:1875-88.

255. Sakai N, Onodera K, Maeyama K, Yanai K, Watanabe T. Effects of (S)-α-fluoromethylhistidine and metoprine on locomotor activity and brain histamine content in mice. Life Sci 1992; 51:397-405.

256. Yokoyama H, Iinuma K, Yanai K, Watanabe T, Sakurai E, Onodera K. Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography. Methods Find Exp Clin Pharmacol 1993; 15:183-8.

257. Yokoyama H, Onodera K, Maeyama K, Yanai K, Iinuma K, Tuomisto L, et al. Histamine levels and clonic convulsions of electrically-induced seizure in mice: the effects of alpha-fluoromethylhistidine and metoprine. Naunyn Schmiedebergs Arch Pharmacol 1992; 346:40-5.

258. Scherkl R, Hashem A, Frey HH. Histamine in brain- -its role in regulation of seizure susceptibility. Epilepsy Res 1991; 10:111-8.

259. Yokoyama H, Onodera K, Iinuma K, Watanabe T. Effect of thioperamide, a histamine H3 receptor antagonist, on electrically induced convulsions in mice. Eur J Pharmacol 1993; 234:129-33.

260. Yokoyama H, Onodera K, Maeyama K, Sakurai E, Iinuma K, Leurs R, et al. Clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, inhibits electrically induced convulsions in mice. Eur J Pharmacol 1994; 260:23-8.

261. Murakami K, Yokoyama H, Onodera K, Iinuma K, Watanabe T. AQ-0145, a newly developed histamine H3 antagonist, decreased seizure susceptibility of electrically induced convulsions in mice. Methods Find Exp Clin Pharmacol 1995; 17 (Suppl C):70-3.

262. Sander K, Kottke T, Stark H. Histamine H3 receptor antagonists go to clinics. Biol Pharm Bull 2008; 31:2163-81.

263. Ryu JH, Yanai K, Watanabe T. Marked increase in histamine H3 receptors in the striatum and substantia nigra after 6-hydroxydopamine-induced denervation of dopaminergic neurons: an autoradiographic study. Neurosci Lett 1994; 178:19-22.

264. Anichtchik OV, Rinne JO, Kalimo H, Panula P. An altered histaminergic innervation of the substantia nigra in Parkinson’s disease. Exp Neurol 2000; 163:20-30.

265. Rinne JO, Anichtchik OV, Eriksson KS, Kaslin J,Tuomisto L, Kalimo H, et al. Increased brain histamine levels in Parkinson’s disease but not in multiple system atrophy. J Neurochem 2002; 81:954-60.

266. Anichtchik OV, Peitsaro N, Rinne JO, Kalimo H,Panula P. Distribution and modulation of histamine H3 receptors in basal ganglia and frontal cortex of healthy controls and patients with Parkinson’s disease. Neurobiol Dis 2001; 8:707-16.

267. Schapira AH, Bezard E, Brotchie J, Calon F, Collingridge GL, Ferger B, et al. Novel pharmacological targets for the treatment of Parkinson’s disease. Nat Rev Drug Discov 2006; 5:845-54.

268. Santini E, Valjent E, Usiello A, Carta M, Borgkvist A, Girault JA, et al. Critical involvement of cAMP/ DARPP-32 and extracellular signal-regulated protein kinase signaling in L-DOPA-induced dyskinesia. J Neurosci 2007; 27:6995-7005.

269. Gomez-Ramirez J, Johnston TH, Visanji NP, Fox SH, Brotchie JM. Histamine H3 receptor agonists reduce L-dopa-induced chorea, but not dystonia, in the MPTP-lesioned nonhuman primate model of Parkinson’s disease. Mov Disord 2006; 21:839-46.

270. McCormick DA. Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog Neurobiol 1992; 39:337-88.

271. Yoshimatsu H. Hypothalamic neuronal histamine regulates body weight through the modulation of diurnal feeding rhythm. Nutrition 2008; 24:827-31.

272. Yoshimoto R, Miyamoto Y, Shimamura K, Ishihara A, Takahashi K, Kotani H, et al. Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus. Proc Natl Acad Sci U S A 2006; 103:13866-71.

273. Nakai T, Kitamura N, Hashimoto T, Kajimoto Y, Nishino N, Mita T, et al. Decreased histamine H1 eceptors in the frontal cortex of brains from patients with chronic schizophrenia. Biol Psychiatry 1991; 30:349-56.

274. Deutsch SI, Rosse RB, Kendrick KA, Fay-McCarthy M, Collins JP, Jr., Wyatt RJ. Famotidine adjunctive pharmacotherapy for schizophrenia: preliminary data. Clin Neuropharmacol 1993; 16:518-24.

275. Martinez MC. Famotidine in the management of schizophrenia. Ann Pharmacother 1999; 33:742-7.

276. Esbenshade TA, Browman KE, Bitner RS, Strakhova M, Cowart MD, Brioni JD. The histamine H3 receptor: an attractive target for the treatment of cognitive disorders. Br J Pharmacol 2008; 154:1166-81.

277. Bertoni S, Ballabeni V, Flammini L, Saccani F,Domenichini G, Morini G, et al. In vitro and in vivo pharmacological analysis of imidazole-free histamine H3 receptor antagonists: promising results for a brainpenetrating H3 blocker with weak anticholinesterase activity. Naunyn Schmiedebergs Arch Pharmacol 2008; 378:335-43.

278. Millan-Guerrero RO, Isais-Millan R, Barreto- Vizcaino S, Gutierrez I, Rivera-Castano L, Trujillo- Hernandez B, et al. Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study. Eur Neurol 2008; 59:237-42.

279. Millan-Guerrero RO, Isais-Millan R. New therapeutic alternatives in migraine prophylaxis using histamine H3 receptor agonists. Gac Med Mex 2008; 144:291-5.

280. Feuerstein TJ. Presynaptic receptors for dopamine,histamine, and serotonin. Handb Exp Pharmacol 2008:289-338.