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2004, Number 2

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Salud Mental 2004; 27 (2)

El polipéptido activador de la adenilato ciclasa de la pituitaria (PACAP): actualización de conocimientos

Mucio-Ramírez S, Miller-Pérez C, Curras-Collazo M, León-Olea M

Language: Spanish
References: 154
Page: 55-69
PDF size: 297.04 Kb.


ABSTRACT

After the discovery of the hypophysiotropic hypothalamic, factors such as the luteinizing hormone releasing factor, thyrotropin hormone, growth hormone and corticotropin, the releasing factors for the follicle stimulating hormone and that of prolactin were characterized. However, some studies showed that few new cells in adenohypophysis would presumably require their hypothalamic regulator. This opened the possibility for the existence of a new hypophysiotropic factor. Eventually in 1998, a pituitary adenylate cyclase activating polypeptide (PACAP) was discovered by Miyata et al. Its name arises from the effect it exerts on pituitary cells by increasing cyclic AMP (cAMP) levels, and consequently originating the release of various hypophysial hormones, i.e., prolactin, oxytocin, vasopressin and growth hormone, among others. It has been reported that PACAP regulates important biological functions in vertebrates, being among the most relevant its role as a hypophysiotropic factor and neuromodulator. Furthermore, PACAP produced vasodilation, bronchodilation, activation of intestinal motility, increase of insulin and histamine secretion, as well as stimulation of cell multiplication and/or differentiation. This review paper provides the most recent information on the diverse physiological roles that PACAP and its receptors exert on the Central Nervous System (CNS) and on other systems. The wide anatomical distribution of this polypeptide and that of its receptors has drawn the interest of various research groups in trying to elucidate the pharmacological effects and biological functions in which PACAP participates. This peptide consists of 38 amino acids and was isolated from ovine hypothalamic extracts. Two biologically active forms exist: one having 38 residues and a truncated one of 27 residues. Both peptides are amidated in their carboxyl terminal. It is widely distributed in SNC, Peripheral Nervous System and in cells of various tissues and organs of different animal species. PACAP belongs to the superfamily secretin/growth hormone (GH)/glucagon/vasoactive intestinal polypeptide (VIP), and from a phylogenetic point of view, it has the most preserved sequence. PACAP shares a highly structural homology with all the peptides belonging to this family, mainly with porcine VIP, showing a 68% homology in its amino terminal portion. The molecular cloning of the complementary DNA of the PACAP-38 precursor of rat, mouse and human showed that the amino acid sequence was 100% identical for all of them. The PACAP sequence has been identified in different vertebrate species and in some invertebrates such as tunicates and annelids. PACAP from these species shows a high degree of identity with human PACAP, the only difference lying in one- to four-amino acids. This amino acid conservation pattern in the various animal species shows the biologic relevance of this neuropeptide. Phylogenetic evidence suggest that the PACAP gene originated from the duplication of an ancestral common gene of the superfamily secretin/GH/glucagon/VIP. Therefore, the general organization of the PACAP gene holds a great similitude with that of VIP and the rest of the members of this superfamily. In 1992 Hosoya et al. cloned the human PACAP gene, which is located in region p11 of chromosome 18. It is formed by 5 exons and 4 introns. Exon 1 codifies a cryptic protein; exon 2, the signal peptide; exon 3, a spacing protein having no apparent function; exon 4 codifies the so-called PRP peptide with no known biological function, and exon 5 codifies PACAP-38. Several groups have cloned the PACAP receptor and its isoforms. Receptors for PACAP belong to a family of receptors coupled to G proteins having 7 transmembranal domains. PACAP produces its biological effects by binding to at least 3 types of receptors PAC-1, VPAC1 and VPAC2. Receptor PAC-1 has the highest binding affinity for PACAP-38 (Kd 0.5 nM) and to a lesser degree for PACAP-27 (Kd 2.0 nM). PACAP is widely distributed in the CNS, peripheral nervous system, and various glands and organs. Anatomical studies showing the distribution of mRNA encoding PACAP and its receptors reported that this neuropeptide and corresponding receptors are expressed very early in mouse embryonic stages. Studies carried out in the CNS of adult rat reported PACAP-38 and PACAP-27 immunoreactive (IR) cells and fibers in cerebellar cortex, hippocampus, septum, thalamus, supraoptic and paraventricular hypothalamic nuclei, median eminence, medulla oblongata and spinal cord. The highest PACAP concentration outside the CNS lies in the testicles of rat and mouse. Other tissues and organs presenting IR cells and fibers are the gastrointestinal tract, pancreas, retina and some sympathetic ganglia, as well as the following glands: hypophysis, adrenal, pineal and salivary.
PACAP fulfills the criteria for being considered a hypophysiotropic factor, since it is present in hypothalamic neurons projecting to the pituitary-portal system; and in the blood circulating in this system, it interacts with specific receptors localized in pituitary cells and regulates them. PACAP stimulates the synthesis and release of LH and FSH in gonadotropic cells. It also stimulates the somadendritic release of oxytocin and vasopressin. In addition, our group demonstrated that PACAP administration enhances 2 to 9 times vasopressin basal release in hypothalamic and hypophyseal slices in vitro. PACAP stimulates melanotropes by increasing POMC genomic expression, and translates its signal through cAMP and inositol phosphate pathways. PACAP increases in a dose dependent manner ±-MSH and ACTH secretions, at 1nM concentrations. PACAP also modulates prolactin release. In neocortical culture cells, it also stimulates the genomic expression of proenkephalin, which is the precursor of leu- and met-enkephalin. This polypeptide co-localizes with various neurotransmitters and/or neuromodulators in neurons, modulating their release or interacting as a whole to regulate a certain function. Among the most widely studied of these substances one may mention catecholamines, melatonin, histamine, serotonin and nitric oxide (NO). PACAP regulates the activity of male and female gonads. It stimulates testosterone secretion in Leydig cells in a dose dependent manner. In Leydig cells, PACAP activates adenylate cyclase and phospholipase C by interacting with receptor PAC-1. PACAP stimulates estradiol and progesterone secretions in the ovary of the rat. These studies and the presence of PAC-1 receptor in the granulosa cells suggest that PACAP may be an autocrine or paracrine regulator of ovarian function. PACAP activates Ca2+ channels, and as a consequence a higher catecholamine release ensues. Similarly, aldosterone secretion is increased; this mineralocorticoid regulates the electrolytic balance via a paracrine mechanism which stimulates the cells in the adrenal cortex. Likewise, it also raises cortisol levels. These findings identify PACAP as a possible adrenal gland neuromodulator in different animal species, and support the hypothesis that PACAP is an important modulator participating in functions related to the hypothalamus-hypophysis-adrenal system. PACAP diminishes nitric oxide production in a dosedependent manner in PC12 cultured cells, probably by the phosphorilation of the enzyme nitric oxide synthase, thus suggesting a regulatory role for PACAP in the activity of this enzyme. This peptide has been considered a neuroprotective factor, since it protects cortical cells and PC12 cells from glutamate cytotoxic effects. During development, PACAP acts as a neurotrophic factor, while in adult brain it acts rather as a neuroprotective agent.
From what has been previously mentioned, PACAP regulates various relevant biological functions in vertebrates. Still, there are many things waiting to be elucidated with regard to this polypeptide. In this review paper we tried to include the most recent information on the participation of this peptide in diverse physiological actions.


REFERENCES

  1. ADAMS BA, LESCHEID DW, VICKERS ED, CRIM LW, SHERWOOD NM: Pituitary adenylate cyclase-activating polypeptide and growth hormone-releasing hormone-like peptide in sturgeon, whitefish, grayling, flounder and halibut: cDNA sequence, exon skipping and evolution. Regul Pept, 15:27-37, 2002.

  2. ANDERSON ST, CURLEWIS JD: PACAP stimulates dopamine neuronal activity in the medial basal hypothalamus and inhibits prolactin. Brain Res, 790(1-P2):343-6, 1998.

  3. ANDERSON ST, SAWANGJAROEN K, CURLEWIS JD: Pituitary adenylate cyclase-activating polypeptide acts within the medial basal hypothalamus to inhibit prolactin and luteinizing hormone secretion. Endocrinology, 137(8):3424-9, 1996.

  4. AOKI Y, IWASAKI Y, KATAHIRA M, OISO Y, SAITO H: Regulation of the rat proopiomelanocortin gene expression in AtT-20 cells. II: Effects of the pituitary adenylate cyclaseactivating polypeptide and vasoactive intestinal polypeptide. Endocrinology, 138(5):1930-4, 1997.

  5. ARIMURA A, SHIODA S: Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction. Fr ont Neuroendocrinol, 16(1):53-88, 1995.

  6. ARIMURA A, SOMOGYVARI-VIGH A, MIYATA A, MIZUNO K, COY DH, KITADA C: Tissue distribution of PACAP as determined by RIA: highly abundant in the rat brain and testes. Endocrinology, 129(5):2787-9, 1991.

  7. ARIMURA A: Pituitary adenylate cyclase activating polypeptide (PACAP): discovery and current status of research. Regul Pept; 37(3):287-303, 1992.

  8. ARIMURA A: Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems. Jpn J Physiol, 48(5):301-31, 1998.

  9. BASAK A, TOURE BB, LAZURE C, MBIKAY M, CHRETIEN M, SEIDAH NG: Enzymic characterization in vitro of recombinant proprotein convertase PC4. Biochem J, (343 Pt) 1:29-37, 1999.

  10. BASILLE M, GONZALEZ BJ, LEROUX P, JEANDEL L, FOURNIER A, VAUDRY H: Localization and characterization of PACAP receptors in the rat cerebellum during development: evidence for a stimulatory effect of PACAP on immature cerebellar granule cells. Neuroscience, 57(2):329-38,1993.

  11. BEAUDET MM, BRAAS KM, MAY V: Pituitary adenylate cyclase activating polypeptide (PACAP) expression in sympathetic preganglionic projection neurons to the superior cervical ganglion. J Neurobiol, 36(3):325-36, 1998.

  12. BOLER J, ENZMANN F, FOLKERS K, BOWERS CY, SCHALLY AV: The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidyl-proline amide. Biochem Biophys Res Comun, 37(4):705-10, 1969.

  13. BOUTILLIER AL, MONNIER D, KOCH B, LOEFFLER JP: Pituitary adenyl cyclase-activating peptide: a hypophysiotropic factor that stimulates proopiomelanocortin gene transcription, and proopiomelanocortin-derived peptide secretion in corticotropic cells. Neuroendocrinology, 60(5):493- 502, 1994.

  14. BRAAS KM, BRANDENBURG CA, MAY V: Pituitary adenylate cyclase-activating polypeptide regulation of AtT- 20/D16v corticotrope cell proopiomelanocortin expression and secretion. Endocrinology, 134(1):186-95, 1994.

  15. BRENNEMAN DE, HAUSER J, PHILLIPS TM: VIP and PACAP release chemokines: A mechanism for neuroprotection from HIV envelope protein toxicity. Regul Pept, 83:42, 1999.

  16. BRENNEMAN DE, HAUSER JM, SPONG C, PHILLIPS TM: Chemokine release is associated with the protective action of PACAP-38 against HIV envelope protein neurotoxicity. Neuropeptides, 36(4):271-80, 2002.

  17. BUSCAIL L, CAMBILLAU C, SEVA C, SCEMAMA JL, DE NEEF P y cols.: Stimulation of rat pancreatic tumoral AR4- 2J cell proliferation by pituitary adenylate cyclase-activating peptide. Gastroenterology, 103(3):1002-8, 1992.

  18. CAMPARD PK, CROCHEMORE C, RENE F, MONNIER D, KOCH B y cols.: PACAP type I receptor activation promotes cerebellar neuron survival through the cAMP/ PKA signaling pathway. DNA Cell Biol, 16:323-333 1997.

  19. CAMPBELL RM, SCANES CG: Evolution of the growth hormone-releasing factor (GRF) family of peptides. Growth Regul, 2: 175-191, 1992.

  20. CAVALLARO S, COPANI A, D’AGATA V, MUSCO S, PETRALIA S y cols.: Pituitary adenylate cyclase-activating polypeptide prevents apoptosis in cultured cerebellar granule neurons. Mol Pharmacol, 50:60-66, 1996.

  21. CHANG JY, KOROLEV VV WANG JZ: Cyclic AMP and pituitary adenylate cyclase-activating polypeptide (PACAP) prevent programmed cell death of cultured rat cerebellar granule cells. Neurosci Lett, 206:181-184,1996.

  22. CHARTREL N, TONON M-C, VAUDRY H, CONLON JM: Primary structure of frog pituitary adenylate cyclaseactivating polypeptide (PACAP) and effects of ovine PACAP on frog pituitary. Endocrinology, 129:3367–3371, 1991.

  23. CHIODERA P, VOLPI R, CAPRETTI L, COIRO V: Effects of intravenously infused pituitary adenylate cyclase-activating polypeptide on arginine vasopressin and oxytocin secretion in man. Neuroreport, 6(11):1490-2, 1995.

  24. COLEMAN DT, BANCROFT C: Pituitary adenylate cyclaseactivating polypeptide stimulates prolactin gene expression in a rat pituitary cell line. Endocrinology, 133(6):2736-42,1993.

  25. DOW RC, BENNIE J, FINK G: Pituitary adenylate cyclaseactivating peptide-38 (PACAP)-38 is released into hypophysial portal blood in the normal male and female rat. J Endocrinol, 142(1):R1-4, 1994.

  26. EDWARDS AV, JONES CT: Adrenal responses to the peptide PACAP in conscious functionally hypophysectomized calves. Am J Physiol, 266(6 Pt 1):E870-6, 1994.

  27. EIPPER BA, STOFFERS DA MAINS RE: The biosynthesis of neuropeptides: Peptide -amidation. Ann Rev Neurosci, 15: 57-85, 1992.

  28. EL-GEHANI F, ZHANG FP, PAKARINEN P, RANNIKKO, A HUHTANIEMI: Gonadotropinindependent regulation of steroidogenesis in the fetal rat testis. Biol Reprod, 58:116-123,1998.

  29. FUJIMIYA M, YAMAMOTO H, KUWAHARA A: Effect of VIP and PACAP on basal release of serotonin from isolated vascularly and luminally perfused rat duodenum. Am J Physiol, 275(4 Pt 1):G731-9, 1998.

  30. FUJIMIYA M, YAMAMOTO H, KUWAHARA A: Effect of VIP and PACAP on vascular and luminal release of serotonin from isolated perfused rat duodenum. Ann N Y Acad Sci, 865:495-502, 1998.

  31. FUKUSHIMA Y, HIKICHI H, MIZUKAMI K, NAGAYAMA T, YOSHIDA M y cols.: Role of endogenous PACAP in catecholamine secretion from the rat adrenal gland Am J Physiol, Regulatory Integrative Comp Physiol, 281:R1562– R1567, 2001.

  32. FUKUSHIMA Y, NAGAYAMA T, KAWASHIMA H, HIKICHI H, YOSHIDA M y cols.: Role of calcium channels and adenylate cyclase in the PACAP-induced adrenal catecholamine secretion. Am J Physiol Regul Integr Comp Physiol, 281(2):R495-501, 2001.

  33. GENG G, GASPO R, TRABELSI F, YAMAGUCHI N: Role of L-type Ca2+ channel in PACAP-induced adrenal catecholamine release in vivo. Am J Physiol, 273(4 Pt 2):R1339-45, 1997.

  34. GHATEI MA, TAKAHASHI K, SUZUKI Y, GARDINER J, JONES PM y cols.: Distribution, molecular characterization of pituitary adenylate cyclase-activating polypeptide and its precursor encoding messenger RNA in human and rat tissues. J Endocrinol, 136(1):159-66, 1993.

  35. GILLARD E, MUSSENDEN H, SNISSARENKO E, LEON-OLEA M, CURRAS-COLLAZO MC: Effects of pacap on vasopressin and excitatory amino acid release in the rat supraoptic nucleus in vitro. Neurosci Abs, 471.5.CDROM, 2002.

  36. GILLARD ER, COBURN CG, BAUCE LG, SNISSARENKO EP, PITTMAN QJ, LEON-OLEA M, CURRAS-COLLAZO MC: Somatodendritic nitric oxide and pacap in son magnocellular neuroendocrine cell (MNC) responses to dehydration. Neurosci Abs, 612.19. CD-ROM, 2003.

  37. GONZALEZ BJ, BASILLE M, VAUDRY D, FOURNIER A VAUDRY H: Pituitary adenylate cyclase-activating polypeptide promotes cell survival and neurite outgrowth in rat cerebellar neuroblasts. Neuroscience, 78:419-430, 1997.

  38. GOTTSCHALL PE, TATSUNO I, MIYATA A, ARIMURA A: Characterization and distribution of binding sites for the hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide. Endocrinology, 127(1):272-7,1990.

  39. GRÄS S, HANNIBAL J, GEORG B FAHRENKRUG J: Transient periovulatory expression of pituitary adenylate cyclase-activating peptide in rat ovarian cells. Endocrinology, 137:4779-4785, 1996.

  40. GRAS S, HEDETOFT C, PEDERSEN SH, FAHRENKRUG J: Pituitary adenylate cyclase-activating peptide stimulates acute progesterone production in rat granulosa/Lutein cells via two receptor subtypes. Biol Reprod, 63(1):206-12, 2000.

  41. GUILLEMIN R, BRAZEAU P, BOHLEN P, ESCH F, LING N, WEHRENBERG WB: Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science, 218(4572):585-7, 1982.

  42. GUO X, WAKADE AR: Differential secretion of catecholamines in response to peptidergic and cholinergic transmitters in rat adrenals. J Physiol (Lond), 475:539–545, 1994.

  43. GUR G, BONFIL D, SAFARIAN H, NAOR Z, YARON Z: Pituitary adenylate cyclase activating polypeptide and neuropeptide Y regulation of gonadotropin subunit gene expression in tilapia: role of PKC, PKA and ERK. Neuroendocrinology, 75(3):164-74, 2002.

  44. GUR G, ROSENFELD H, MELAMED P, MEIRI I, ELIZUR A, YARON Z: Tilapia glycoprotein hormone alpha subunit: cDNA cloning and hypothalamic regulation. Mol Cell Endocrinol, 182(1):49-60, 2001.

  45. HANNIBAL J: Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohistochemical and in situ hybridization study. J Comp Neurol, 453(4):389- 417, 2002.

  46. HANNIBAL J, FAHRENKRUG J: Expression of pituitary adenylate cyclase activating polypeptide (PACAP) gene by rat spermatogenic cells. Regul Pept, 55:111-5, 1995.

  47. HANNIBAL J, FAHRENKRUG J: Pituitary adenylate cyclase-activating polypeptide in intrinsic and extrinsic nerves of the rat pancreas. Cell Tissue Res, (1):59-70, 2000.

  48. HARTFIELD PJ, BILNEY AJ, MURRAY AW: Neurotrophic factors prevent ceramide-induced apoptosis downstream of c-Jun N-terminal kinase activation in PC12 cells. J Neurochem, 71(1):161-9, 1998.

  49. HASHIMOTO H, HAGIHARA N, KOGA K, YAMAMOTO K, SHINTANI N y cols.: Synergistic induction of pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression by nerve growth factor and PACAP in PC12 cells. J Neurochem, 74:501-507, 2000.

  50. HASHIMOTO H, ISHIHARA T, SHIGEMOTO R, MORI K, NAGATA S: Molecular cloning and tissue distribution of a receptor for pituitary adenylate cyclase-activating polypeptide. Neuron, 11:333-42, 1993.

  51. HASHIMOTO H, YAMAMOTO K, HAGIGARA N, OGAWA N, NISHINO A y cols.: cDNA cloning of a mouse pituitary adenylate cyclase-activating polypeptide receptor. Biochim Biophys Acta, 1281(2):129-33, 1996.

  52. HEINDEL JJ, POWELL CJ, PASCHALL CS, ARIMURA A, CULLER MD: A novel hypothalamic peptide, pituitary adenylate cyclase activating peptide, modulates Sertoli cell function in vitro. Biol Reprod, 47(5):800-6, 1992.

  53. HEINDEL JJ, SNEEDEN J, POWELL CJ, DAVIS B, CULLER MD: A novel hypothalamic peptide, pituitary adenylate cyclase-activating peptide regulates the function of rat granulosa cells in vitro. Biol Reprod, 54:523–530, 1996.

  54. HOSOYA M, KIMURA C, OGI K, OHKUBO S, MIYAMOTO Y, KUGOH H y cols.: Structure of the human pituitary adenylate cyclase-activating polypeptide (PACAP) gene. Biochim Biophys Acta, 1129:199-206, 1992.

  55. HOSOYA M, ONDA H, OGI K, MASUDA Y, MIYAMOTO Y, OHTAKI T y cols.: Molecular cloning and functional expression of rat cDNAs encoding the receptor for pituitary adenylate cyclase activating polypeptide (PACAP). Biochem Biophys Res Commun, 194(1):133-43, 1993.

  56. HYDE JF, MURAI I, BEN-JONATHAN N: Differential effects of pituitary stalk-section on posterior pituitary and hypothalamic contents of prolactin-releasing factor, oxytocin, dopamine and beta-endorphin. Neuroendocrinology, 48(3):314-9, 1988.

  57. INOOKA H, OHTAKI T, KITAHARA O, IKEGAMI T, ENDO S y cols.: Conformation of a peptide ligand bound to its G-protein coupled receptor. Nat Struct Biol, 8(2):161-5, 2001.

  58. ISOBE K, NAKAI T, TAKUWA Y: Ca21-dependent stimulatory effect of pituitary adenylate cyclase-activating polypeptide on catecholamine secretion from cultured porcine adrenal medullary chromaffin cells. Endocrinology, 132:1757–1765, 1993.

  59. JAMEN F, ALONSO G, SHIBUYA I, WIDMER H, VACHER CM y cols.: Impaired somatodendritic responses to pituitary adenylate cyclase-activating polypeptide (PACAP) of supraoptic neurones in PACAP type I -receptor deficient mice. J Neuroendocrinol, 15(9):871-81, 2003.

  60. JIANG Y, LI WS, XIE J, LIN HR: Sequence and Expression of a cDNA Encoding Both Pituitary Adenylate Cyclase Activating Polypeptide and Growth Hormone-releasing Hormone in Grouper (Epinephelus coioides). Acta Biochimica et Biophysica SINICA, 35:864-872, 2003.

  61. JUST L, MORL F, BARMANN C, OLENIK C, MEYER DK: Evidence for cell specific regulation by PACAP38 of the proenkephalin gene expression in neocortical cells. Glia, 30(3):242-52, 2000.

  62. KATAYAMA T, NAKASHIMA M, KYAN H, MURAKAMI N, KURODA H: A role of pituitary adenylate cyclase activating polypeptide (PACAP) as a regulator of paracrine interactions between folliculo-stellate cells and gonadotropes through the control of activin-follistatin interactions. J Vet Med Sci, 62(7):731-6, 2000.

  63. KAWAI K, YOKOTA C, OHASHI S, ISOBE K, SUZUKI S y cols.: Pituitary adenylate cyclase-activating polypeptide: effects on pancreatic-adrenal hormone secretion and glucoselipid metabolism in normal conscious dogs. Metabolism, 43(6):739-44,1994.

  64. KIMURA C, OHKUBO S, OGI K, HOSOYA M, ITOH Y y cols.: A novel peptide which stimulates adenylate cyclase: molecular cloning and characterization of the ovine and human cDNAs. Biochem Biophys Res Commun, 166(1):81-9, 1990.

  65. KIMURA S, OHSHIGE Y, LIN L, OKUMURA T, YANAIHARA C y cols.: Localization of pituitary adenylate cyclase-activating polypeptide (PACAP) in the hypothalamuspituitary system in rats: light and electron microscopic immunocytochemical studies. J Neuroendocrinol, 6(5):503-7, 1994.

  66. KOCH B, LUTZ-BUCHER B: Pituitary adenylate cyclaseactivating polypeptide (PACAP) stimulates cyclic AMP formation as well as peptide output of cultured pituitary melanotrophs and AtT-20 corticotrophs. Regul Pept, 38(1):45-53, 1992.

  67. KOTANI E, USUKI S, KUBO T: Detection of pituitary adenylate cyclase-activating polypeptide messenger ribonucleic acids (PACAP mRNA) and PACAP receptor mRNA in the rat ovary. Biomed Res, 18:199–204, 1997a.

  68. KOTANI E, USUKI S, KUBO T: Rat corpus luteum expresses both PACAP and PACAP type IA receptor mRNAs. Peptides, 18(9):1453-5, 1997b.

  69. KOVES K, KANTOR O, SCAMMELL JG, ARIMURA A: PACAP colocalizes with luteinizing and follicle-stimulating hormone immunoreactivities in the anterior lobe of the pituitary gland. Peptides, 19(6):1069-72, 1998.

  70. KOVES K, MOLNAR J, KANTOR O, GORCS TJ, LAKATOS A, ARIMURA A: New aspects of the neuroendocrine role of PACAP. Ann N Y Acad Sci, 805:648-54. 1996.

  71. LAMOUCHE S, YAMAGUCHI N: Role of PAC(1) receptor in adrenal catecholamine secretion induced by PACAP and VIP in vivo. Am J Physiol Regul Integr Comp Physiol,

  72. LEGRADI G, SHIODA S, ARIMURA A: Pituitary adenylate cyclase-activating polypeptide-like immunoreactivity in autonomic regulatory areas of the rat medulla oblongata. Neurosci Lett, 176(2):193-6, 1994.

  73. LEON-OLEA M, MUCIO-RAMIREZ S, SANCHEZ-ISLAS E, ANGELES-ESCUDERO A y cols.: Immunoreactivity to PACAP and NADPH-d activity are increased in osmotic activated rats. Neurosci Abs, 175.7 CDROM, 2002.

  74. LI M, MBIKAY M, ARIMURA A: Pituitary adenylate cyclase-activating polypeptide precursor is processed solely by prohormone convertase 4 in the gonads. Endocrinology, 141(10):3723-30, 2000a.

  75. LI M, MBIKAY M, NAKAYAMA K, MIYATA A, ARIMURA A: Prohormone convertase PC4 processes the precursor of PACAP in the testis. Ann N Y Acad Sci, 921:333-9 2000b.

  76. LI M, SHUTO Y, SOMOGYVARI-VIGH A ARIMURA A: Prohormone convertases 1 and 2 process proPACAP and generate matured, bioactive PACAP38 and PACAP27 in transfected rat pituitary GH4C1 Cells. Neuroendocrinology, 69:217-226, 1999.

  77. LI S, GRINEVICH V, FOURNIER A, PELLETIER G: Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on gonadotropin-releasing hormone and somatostatin gene expression in the ratbrain. Brain Res Mol Brain Res, 41(1-2):157-62, 1996.

  78. LIU W, MOLLER M: Innervation of the rat pineal gland by PACAP-immunoreactive nerve fibers originating in the trigeminal ganglion: a degeneration study. Cell Tissue Res, 301(3):369-73, 2000.

  79. LUMPKIN MD, MOLTZ JH, YU WH, SAMSON WK, MCCANN SM: Purification of FSH-releasing factor: its dissimilarity from LHRH of mammalian, avian, and piscian origin. Brain Res Bull, 18(2):175-8, 1987.

  80. MATSUO H, BABA Y, NAIR RM, ARIMURA A, SCHALLY AV: Structure of the porcine LH-and FSH-releasing hormone. I. The proposed amino acid sequence. Biochem Biophys Res Comun, 43(6):1334-9, 1971.

  81. MAZZOCCHI G, MALENDOWICZ LK, REBUFFAT P, GOTTARDO L, NUSSDORFER GG: Expression and function of vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and their receptors in the human adrenal gland. J Clin Endocrinol Metab, 87(6):2575-80, 2002.

  82. MCRORY JE, PARKER RL, SHERWOOD NM: Expression and alternative processing of a chicken gene encoding both growth hormone-releasing hormone (GRF) and pituitary adenylate cyclaseactivating polypeptide (PACAP). DNA Cell Biol, 16:95–102, 1997.

  83. MIYATA A, ARIMURA A, DAHL RR, MINAMINO N, UEHARA A y cols.: Isolation of a novel 38 residuehypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun, 164:567-74, 1989.

  84. MIYATA A, JIANG L, DAHL RD, MINAMINO N, KITADA C y cols.: Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the Pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP- 38). Biochem Biophys Res Commun, 170:643-648, 1990.

  85. MOLLER K, SUNDLER F: Expression of pituitary adenylate cyclase activating peptide (PACAP) and PACAP type I receptors in the rat adrenal medulla. Regul Pept, 63(2-3):129-39, 1996.

  86. MOLLER M, FAHRENKRUG J, HANNIBAL J: Innervation of the rat pineal gland by pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive nerve fibres. Cell Tissue Res, 296(2):247-57, 1999.

  87. MONTERO M, YON L, KIKUYAMA S, DUFOUR S, VAUDRY H: Molecular evolution of the growth hormonereleasing hormone/pituitary adenylate cyclase activating polypeptide gene family. Functional implication in the regulation of growth hormone secretion. J Mol Endocrinol, 25(2):157-68, 2000.

  88. MORI T, KAWASHIMA T, BEPPU Y TAKAGI K: Histamine release induced by pituitary adenylate cyclase activating polypeptide from rat peritoneal mast cells. Arzneimittelforschung, 44:1044-1046, 1994.

  89. MORIO H, TATSUNO I, TANAKA T, UCHIDA D, HIRAI A y cols.: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neurotrophic factor for cultured rat cortical neurons. Ann N Y Acad Sci, 26;(805):476-81, 1996.

  90. MORROW JA, LUTZ EM, WEST KM, FINK G, HARMAR AJ: Molecular cloning and expression of a cDNA encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP). FEBS Lett, 329(1-2):99-105, 1993.

  91. MUCIO-RAMIREZ S, CURRAS-COLLAZO M, LEONOLEA M: Immunoreactivity to PAC-1 receptor and PACAP are increased in the supraoptic and paraventricular nuclei in osmotic activated rats. IBRO Abs, 3226. CD-ROM, 2003.

  92. MURAKAMI Y, KOSHIMURA K, YAMAUCHI K, NISHIKI M y cols.: Roles and mechanisms of action of pituitary adenylate cyclase-activating polypeptide (PACAP) in growth hormone and prolactin secretion. Endocr J, 48(2):123-32, 2001.

  93. NAGY G, MULCHAHEY JJ, SMYTH DG, NEILL JD: The glycopeptide moiety of vasopressin-neurophysin precursor is neurohypophysial prolactin releasing factor. Biochem Biophys Res Comun, 151(1):524-9, 1988.

  94. NAKAHARA K, ABE Y, MURAKAMI T, SHIOTA K, MURAKAMI N: Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in melatonin release via the specific receptor PACAP-r1, but not in the circadian oscillator, in chick pineal cells. Brain Res, 939:19-25, 2002.

  95. NERI G, ANDREIS PG, PRAYER-GALETTI T, ROSSI GP y cols.: Pituitary adenylate-cyclase activating peptide enhances aldosterone secretion of human adrenal gland: evidence for an indirect mechanism, probably involving the local release of catecholamines. J Clin Endocrinol Metab, 81(1):169-73, 1996.

  96. NOMURA M, UETA Y, SERINO R, YAMAMOTO Y, SHIBUYA I, YAMASHITA H: Effects of centrally administered pituitary adenylate cyclase-activating. polypeptide on c-fos gene expression and heteronuclear RNA for vasopressin in rat paraventricular and supraoptic nuclei. Neuroendocrinolgy, 69(3):167-80, 1999.

  97. NUSSDORFER GG, MALENDOWICZ LK: Role of VIP, PACAP, and related peptides in the regulation of the hypothalamo-pituitary-adrenal axis. Peptides, 19(8):1443-67, 1998.

  98. O’FARRELL M, MARLEY PD: Multiple calcium channels are required for pituitary adenylate cyclase-activating polypeptideinduced catecholamine secretion from bovine cultured adrenal chromaffin cells. Naunyn Schmiedebergs Arch Pharmacol, 356: 536–542, 1997.

  99. ODUM L, PETERSEN LJ, SKOV PS, EBSKOV LB: Pituitary adenylate cyclase-activating polypeptide (PACAP) is localized in human dermal neurons and causes histamine release from skin mast cells. Inflamm Res, 47:488-492, 1998.

  100. OGI K, KIMURA C, ONDA H, ARIMURA A, FUJINO M: Molecular cloning and characterization of cDNA for the precursor of rat pituitary adenylate cyclase activating polypeptide (PACAP). Biochem Biophys Res Commun, 173(3):1271-9, 1990.

  101. 101.OGI K, MIYAMOTO Y, MASUDA Y, HABATA Y, HOSOYA M y cols.: Molecular cloning and functional expression of a cDNA encoding a human pituitary adenylate cyclase activating polypeptide receptor. Biochem Biophys Res Commun, 196:1511-21, 1993.

  102. 102.OHKUBO S, KIMURA C, OGI K, OKAZAKI K, HOSOYA M y cols.: Primary structure and characterization of the precursor to human pituitary adenylate cyclase activating polypeptide. DNA Cell Biol, 11:21–30, 1992.

  103. 103.OKAMURA H, MIYAGAWA A, TAKAGI H, ESUMI H y cols.: Co-existence of PACAP and nitric oxide synthase in the rat hypothalamus. Neuroreport, 5:1177-80, 1994.

  104. 104.OKAZAKI K, ITOH Y, OGI K, OHKUBO S, ONDA H: Characterization of murine PACAP mRNA. Peptides, 16:1295–1299, 1995.

  105. 105.OKAZAKI K, KIMURA C, KOSAKA T, WATANABE T, OHKUBO S y cols.: Expression of human pituitary adenylate cyclase-activating polypeptide (PACAP) cDNA in CHO cells and characterization of the products. FEBS Lett, 298:49- 56, 1992.

  106. 106.OLSSON C, HOLMGREN S: PACAP and nitric oxide inhibit contractions in the proximal intestine of the atlantic cod, Gadus morhua. J Exp Biol, 203 Pt 3:575-83, 2000.

  107. 107.ONOUE S, ENDO K, YAJIMA T, KASHIMOTO K: Pituitary adenylate cyclase activating polypeptide regulates the basal production of nitric oxide in PC12 cells. Life Sci, 71(2):205-14, 2002.

  108. 108.ORTMANN O, ASMUS W, DIEDRICH K, SCHULZ KD, EMONS G: Interactions of ovarian steroids with pituitary adenylate cyclase-activating polypeptide and GnRH in anterior pituitary cells. Eur J Endocrinol, 140(3):207-14. 1999.

  109. 109.PISEGNA JR, WANK SA: Molecular cloning and functional expression of the pituitary adenylate cyclase-activating polypeptide type I receptor. Proc Natl Acad Sci, 90(13):6345-9, 1993.

  110. 110.POHL M, WANK SA: Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard. Relationship to vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide and glucagon-like peptide 1 and evidence against the existence of mammalian homologues.J Biol Chem, 273:9778–9784, 1998.

  111. 111.RADZIKOWSKA M, WASILEWSKA-DZIUBINSKA E, BARANOWSKA B: The stimulatory effect of VIP and PACAP on adrenal aldosterone release. Ann N Y Acad Sci, 865:482-5, 1998

  112. 112.RAWLINGS SR, HEZAREH M: Pituitary adenylate cyclaseactivating polypeptide (PACAP) and PACAP/vasoactive intestinal polypeptide receptors: actions on the anterior pituitary gland. Endocr Rev, 17(1):4-29, 1996.

  113. 113.REGLODI D, LENGVARI I, SZELIER M, VIGH S, ARIMURA A: Distribution of PACAP-like immunoreactivity in the nervous system of oligochaeta. Peptides, 21(2):183-8, 2000.

  114. 114.RENE F, MONNIER D, GAIDDON C, FELIX JM, LOEFFLER JP: Pituitary adenylate cyclase-activating polypeptide transduces through cAMP/PKA and PKC pathways and stimulates proopiomelanocortin gene transcription in mouse melanotropes. Neuroendocrinology, 64(1):2-13. 1996.

  115. 115.RIBELAYGA C, PEVET P SIMONNEAUX V: Adrenergic and peptidergic regulations of hydroxyindole-Omethyltransferase activity in rat pineal gland. Brain Res, 777:247-250, 1997.

  116. 116.ROMANELLI F, FILLO S, ISIDORI A, CONTE D: Pituitary adenylate cyclase-activating polypeptide regulates rat Leydig cell function in vitro. Neuropeptides, 31(4):311-7, 1997.

  117. 117.ROMANO D, MAGALON K, CIAMPINI A, TALET C y cols.: Differential involvement of the Ras and Rap1 small GTPases in vasoactive intestinal and pituitary adenylyl cyclase activating polypeptides control of the prolactin gene. J Biol Chem, 278:51386-94, 2003.

  118. 118.ROSSATO M, NOGARA A, GOTTARDELLO F, BORDON P, FORESTA C: Pituitary adenylate cyclase-activating polypeptide stimulates rat Leydig cell steroidogenesis through a novel transduction pathway. Endocrinology, 138:3228-3235, 1997.

  119. 119.SCHMIDT-CHOUDHURY A, FURUTA GT, GALLI SJ, SCHMIDT WE WERSHIL BK: Mast cells contribute to PACAP-induced dermal oedema in mice. Regul Pept, 82:65-69, 1999a.

  120. 120.SCHMIDT-CHOUDHURY A, MEISSNER J, SEEBECK J, GOETZL EJ y cols.: Stem cell factor influences neuroimmune interactions: The response of mast cells to pituitary adenylate cyclase-activating polypeptide is altered by stem cell factor. Regul Pept, 83:73-80, 1999b.

  121. 121.SCHOMERUS C, LAEDTKE E, OLCESE J, WELLER JL y cols.: Signal transduction and regulation of melatonin synthesis in bovine pinealocytes: impact of adrenergic, peptidergic and cholinergic stimuli. Cell Tissue Res, 309:417-28, 2002.

  122. SEEBECK J, SCHMIDT WE, KILBINGER H, NEUMANN J y cols.: PACAP induces bradycardia in guinea-pig heart by stimulation of atrial cholinergic neurones. Naunyn Schmiedebergs Arch Pharmacol, 354:424-430, 1996.

  123. SEIDAH NG, DAY R, MARCINKIEWICZ M CHRETIEN M: Precursor convertases: An evolutionary ancient, cellspecific, combinatorial mechanism yielding diverse bioactive peptides and proteins. Ann N Y Acad Sci, 839:9-24, 1998.

  124. SEKI T, IZUMI S, SHIODA S, ZHOU CJ, ARIMURA A, KOIDE R: Gene expression for PACAP receptor mRNA in the rat retina by in situ hybridization and in situ RT-PCR. Ann N Y Acad Sci, 921:366-9, 2000.

  125. 125.SEKIYA K, NAGASAKI H, OZAKI N, SUZUKI A, MIURA Y, OISO Y: Pituitary adenylate cyclase-activating polypeptide prevents cytokine-induced cytotoxicity via inhibition of inducible nitric oxide synthase expression in beta TC cells. Biochem Biophys Res Commun, 278(1):211-6, 2000.

  126. 126.SHEWARD WJ, LUTZ EM, COPP AJ, HARMAR AJ: Expression of PACAP, and PACAP type 1 (PAC-1) receptor mRNA during development of the mouse embryo. Brain Res Dev Brain Res, 109(2):245-53, 1998.

  127. 127.SHIODA S, LEGRADI G, LEUNG WC, NAKAJO S, NAKAYA K, ARIMURA A: Localization of pituitary adenylate cyclase-activating polypeptide and its messenger ribonucleic acid in the rat testis by light and electron microscopic immunocytochemistry and in situ hybridization. Endocrinology, 135:818–825, 1994.

  128. 128.SHOGE K, MISHIMA HK, SAITOH T, ISHIHARA K y cols.: Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons. Brain Res, 839:66-73, 1999.

  129. 129.SHUTO Y, UCHIDA D, ONDA H, ARIMURA A: Ontogeny of pituitary adenylate cyclase activating polypeptide and its receptor mRNA in the mouse brain. Regul Pept, 67(2):79-83, 1996

  130. SILVEIRA MS, COSTA MR, BOZZA M, LINDEN R: Pituitary adenylyl cyclase-activating polypeptide prevents induced cell death in retinal tissue through activation of cyclic AMP-dependent protein kinase. J Biol Chem, 277:16075-80. 2002.

  131. 131.SIMONNEAUX V, OUICHOU A PEVET P: Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates melatonin synthesis from rat pineal gland. Brain Res, 603:148-152,1993.

  132. 132.SOMOGYVARI-VIGH A, REGLODI D, LI M, LENGVARI I, VIGH S, ARIMURA A: Tissue distribution of PACAP27 and -38 in oligochaeta: PACAP27 is the predominant form in the nervous system of Lumbricus polyphemus. Peptides, 21:1185-91, 2000.

  133. SQUIRE, FLOYD E, BLOOM SK, MCCONNELL J y cols.: Fundamental Neuroscience, 2nd Ed. Academic Press, San Diego, 2003.

  134. 134.SUZUKI N, HARADA M, HOSOYA M, FUJINO M: Enhanced production of pituitary adenylate-cyclaseactivating polypeptide by 1, N6-dibutyryladenosine 3',5'- monophosphate, phorbol 12-myristate 13-acetate and by the polypeptide itself in human neuroblastoma cells, IMR- 32. Eur J Biochem, 223:147-153, 1994.

  135. 135.TAKAHASHI K, TOTSUNE K, MURAKAMI O, SATOH F, SONE M y cols.: Pituitary adenylate cyclase activating polypeptide (PACAP)-like immunoreactivity in human hypothalamus: co-localization with arginine vasopressin. Regul Pept, 50(3):267-75, 1994.

  136. 136.TANAKA K, SHIBUYA I, HARAYAMA N, NOMURA M, KABASHIMA N y cols.: Pituitary adenylate cyclaseactivating polypeptide potentiation of Ca2+ entry via protein kinase C and A pathways in melanotrophs of the pituitary pars intermedia of rats. Endocrinology, 138(10):4086-95, 1997.

  137. 137.TANAKA K, SHIBUYA I, NAGAMOTO T, YAMASHITA H, KANNO T: Pituitary adenylate cyclase-activating polypeptide causes rapid Ca21 release from intracellular stores and long lasting Ca21 influx mediated by Na1 influxdependent membrane depolarization in bovine adrenal chromaffin cells. Endocrinology, 137:956–966, 1996.

  138. 138.THOMAS GB, CUMMINS JT, GRIFFIN N, CLARKE I: Effect and site of action of hypothalamic neuropeptides on prolactin release in sheep. J Neuroendocrinology, 48(3):252-7, 1988.

  139. 139.TOHEI A, MATSUZAKI M, KOGO H: Antagonist of pituitary adenylate cyclase activating polypeptide suppresses prolactin secretion without changing the activity of dopamine neurons in lactating rats. Neuroendocrinology, 73(1):68-74, 2001.

  140. 140.UEMURA S, POMPOLO S, FURNESS JB, HARDY KJ: Nitric oxide synthase in neurons of the human gall-bladder and its colocalization with neuropeptides. J Gastroenterol Hepatol, 12(3):257-65. 1997.

  141. 141.VALE W, SPIESS J, RIVIER C, RIVIER J: Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science, 213(4514):1394-7, 1981.

  142. 142.VARGAS MA, BOURDAIS J, SANCHEZ S, URIOSTEGUI B, MORENO E y cols.: Multiple hypothalamic factors regulate pyroglutamyl peptidase II in cultures of adenohypophyseal cells: role of the cAMP pathway. J Neuroendocrinol, 10(3):199-206, 1998.

  143. 143.VAUDRY D, FALLUEL-MOREL A, BASILLE M, PAMANTUNG TF y cols.: Pituitary adenylate cyclaseactivating polypeptide prevents C2-ceramide-induced apoptosis of cerebellar granule cells. J Neurosci Res, 72(3):303-16, 2003.

  144. 144.VAUDRY D, GONZALEZ BJ, BASILLE M, PAMANTUNG TP y cols.: Pituitary adenylate cyclase activating polypeptide (PACAP) promotes cerebellar granule cell survival through inhibition of caspase-3 activity (Abstract). FENS 2000, Fédération of European Neuroscience Societies, June 24-28, Brighton 2000.

  145. 145.VAUDRY, GONZALEZ J, BASILLE M, YON L, FOURNIER A, VAUDRY H:. Pituitary adenylate cyclaseactivating polypeptide and its receptors: From structure to functions. Pharmacological Reviews, 52:269-324, 2000.

  146. 146.VILLALBA M, BOCKAERT J, JOURNOT L: Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway. J Neurosci, 17:83-90,1997.

  147. 147.WATANABE T, MASUO Y, MATSUMOTO H, SUZUKI N, OHTAKI T y cols.: Pituitary adenylate cyclase activating polypeptide provokes cultured rat chromaffin cells to secrete adrenaline. Biochem Biophys Res Commun, 182:403–411, 1992.

  148. 148.WATANABE T, SHIMAMOTO N, TAKAHASHI A, FUJINO M: PACAP stimulates catecholamine release from adrenal medulla: a novel noncholinergic secretagogue. Am J Physiol, 269(5 Pt 1):E903-9, 1995.

  149. 149.WEST AP, MCKINNELL C, SHARPE RM, SAUNDERS PTK: Pituitary adenylate cyclase-activating polypeptide can regulate testicular germ cell protein synthesis in vitro. J Endocrinol, 144:215-223, 1995.

  150. 150.WINTERS SJ, TSUJII T, ATTARDI B: Effects of GnRH and PACAP on gonadotropin secretion and subunit messenger RNAs. Ann N Y Acad Sci, 805:343-52, 1996.

  151. 151.YAMAGUCHI N, FUKUSHIMA Y: PACAP enhances stimulation-induced norepinephrine release in canine pancreas in vivo. Can J Physiol Pharmacol, 76(7-8):788-97, 1998.

  152. 152.YON L, FEUILLOLEY M, CHARTREL N, ARIMURA A y cols.: Localization, characterization and activity of pituitary adenylate cyclase-activating polypeptide in the frog adrenal gland. J Endocrinol, 139(2):183-94, 1993.

  153. YUWILER A, BRAMMER GL, BENNETT BL: Interaction between adrenergic and peptide stimulation in the rat pineal: Pituitary adenylate cyclase-activating peptide. J Neurochem, 64:2273-2280, 1995.

  154. 154.ZHONG Y, KASSON BG: Pituitary adenylate cyclaseactivating polypeptide stimulates steroidogenesis and adenosine 3',5'-monophosphate accumulation in cultured rat granulosa cells. Endocrinology, 135:207–213, 1994.




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