Mayas MD, Ramírez-Expósito MJ, Cobo M, Camacho B, García MJ, Carrera P, Martínez-Martos JM

Idioma: Español
Referencias bibliográficas: 41
Paginas: 200-205
Archivo PDF: 52.09 Kb.

RESUMEN

Objetivo: las actividades aspartato aminopeptidasa (AspAP) y glutamato aminopeptidasa (GluAP), denominadas conjuntamente actividad aminopeptidasa A (APA), ejercen actividad angiotensinasa debido a su relación con el metabolismo de las angiotensinas en el sistema renina angiotensina cerebral (SRAc). Puesto que el alcohol es una droga de abuso que altera diferentes e importantes sistemas neurotransmisores/neuromoduladores, induciendo una amplia variedad de daños neurológicos, el propósito del presente trabajo es analizar la influencia de la ingesta crónica de etanol (15%; 30 días) sobre la actividad APA. Material y métodos: la APA se midió en sinaptosomas de corteza frontal de ratón, utilizando aspartato- y glutamato-β-naftilamida como sustratos, en condiciones basales y despolarizantes (K+ 25 mM), en presencia y ausencia de calcio en el medio de incubación. Resultados: mientras que el etanol disminuye la actividad APA en condiciones despolarizantes en presencia de calcio y en ausencia de calcio en condiciones basales, la despolarización incrementa los niveles de la actividad APA. Conclusiones: los resultados ponen de manifiesto la existencia de cambios en la actividad angiotensinasa de la corteza frontal de ratones tras la administración de etanol. Estos cambios estarían relacionados con modificaciones en el metabolismo de la angiotensinas del SRAc, por lo que se podría afirmar que el etanol potencia los efectos en la regulación del flujo sanguíneo local o el balance de fluidos y electrolitos.

REFERENCIAS (EN ESTE ARTÍCULO)

1. McKeon UG, O’Connor B. Mamalian pyroglutamyl-peptidase I. In Barret AJ, Rawlings ND, Woesnner JF, eds. Handbook of proteolytic enzimes. Londres: Academic Press. 1998.

2. McDonald Barret. Mamalian proteases: a glossary and bibliography. Academic press London 1986

3. Ahmad S, Ward PE. Role of aminopeptidase activity in the regulation of the pressor activity of circulating angiotensins. J Pharmacol Exp Ther 1990; 252: 643-50.

4. Leung PS. The peptide hormone angiotensin II: its new functions in tissues and organs. Curr Prot Peptide Sci 2004; 5: 267-73.

5. Lavoie JL, Sigmund CD. Minireview: overview of the reninangiotensin system – an endocrine and paracrine system. Endocrinol 2003; 144: 2179-83.

6. Wang J, Cooper MD. Glutamyl aminopeptidase. En Barret AJ, Rawlings ND, Woesnne JF, eds. Handbook of proteolityc enzymes. Londres. Academic Press. 1998.

7. Chansel D, Ardaillou R. Active metabolites derived from angiotensin II. Nephrologie 1998; 19: 427-32.

8. Ardaillou R. Active fragments of ang II: enzymatic pathways of synthesis and biological effects. Curr Opin Nephrol Hypertens 1997; 6 8-34.

9. Llorens-Cortes C. Identification of metabolic pathways of brain angiotensin II and angiotensin III: Predominant role of angiotensin III in the control of vasopressin secretion. C R Seances Soc Biol Fil 1998; 192: 607-18.

10. Reaux A, Fournie-Zaluski MC, David C, Zini S, Roques BP, Corvol P, et al. Aminopeptidase A inhibitors as potential central antihypertensive agents. Proc Natl Acad Sci USA 1999; 96: 13415-20.

11. Kim S, Iwao H. molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 2000; 52: 11-34.

12. Zhuo J, Moeller I, Jenkins T, Chai SY, Allen AM, Oishi M, et al. Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2, and AT4 receptors. J Hypertens 1998; 16: 2027-37.

13. Reaux A, Fournie-Zaluski MC, Llorens-Cortes C. Angiotensin III: A central regulator of vasopressin release and blood pressure. Trends Endocrinol Metab 2001; 12: 157-62.

14. Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 1994; 330: 613-22.

15. Martínez-Martos JM, Ramírez-Expósito MJ, Arrazola-Saniger M, Ramírez-Huertas JM. Neurotoxicidad de aminoácidos excitatorios y sistema nervioso central. Rev Clin Esp 1996; 196: 113-8.

16. Bradford MM. A rapid and sensitive method for quantification of microgram quantities of protein-dye binding. Anal Biochem 1976; 72: 248-54.

17. Powrozek TA, Sori Y, Singh RP, Zhou FC. Neurotransmitters and substances of abuse: effects on adult neurogenesis. Curr Neurovasc Ress 2004 ;1: 251-60;

18. Slawecki JC, Jiménez-Vasquez P, Mathes AA, Ehlers CL. Effect of etanol on brain neuropeptides in adolescent and adult rats. J Stud Alcohol 2005; 66: 46-52.

19. Martínez-Martos JM, Ramírez-Expósito MJ, Mayas-Torres MD, García-López MJ, Ramírez-Sánchez M. Utility of the 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to measure mitochondrial activity in K+- and ATP-stimulated rodent cortex synaptosomes. Neurosci Res Commun 2000; 27: 103-7.

20. Mayas MD, Ramírez-Expósito MJ, García MJ, Ramírez M, Martínez-Martos JM. Ethanol modifies differently aspartyl- and glutamyl-aminopeptidase activities in Mouse frontal cortex synaptosomes.

21. Sánchez-Amate MC, Carrasco MP, Zurera JM, Segovia JL, Marco C. Persistence of the effects of ethanol in vitro on the lipid order and enzyme activities of chick-liver membranes. Eur J Pharmacol 1995; 292: 215-21.

22. Diamond I, Gordon AS. Cellular and molecular neuroscience of alcoholism. Physiol Rev 1997; 77: 1-20.

23. Woodward JJ. Overview of the effects of alcohol on the cerebral nervous system. Neurochem Int 1999; 35: 93-4.

24. 24.Wirkner K, Poelchen W, Köles L, Muhlberg K, Scheibler P, Allgaier C, et al. Ethanol-induced inhibition of NMDA receptor channels. Neurochem Int 1999; 35: 153-62.

25. Grobin AC, Papadeas ST, Morrow AL. Regional variations in the effects of chronic ethanol administration on GABAA receptor expression: Potential mechanism. Neurochem 2000;37:453-61.

26. Lovinger DM. Alcohols and neurotransmitters gated ion channels: past, present and future. Naunyn-Schmiedebergs Arch Pharmacol 1997; 356: 267-82.

27. Crews FT. Morrow AL, Criswell H, Breese G. Effects of ethanol on ion channels. Int Rev Neurobiol 1996; 39: 283-367.

28. Shah J, Pant HC. Spontaneous calcium release induced by ethanol in the isolated rat brain microsomes. Brain Res 1988; 474: 94-9.

29. Mayas MD, Ramírez-Expósito MJ, García MJ, Tsuboyama G, Ramírez M, Martínez-Martos JM. Calcium-dependent modulation by ethanol of mouse sinaptosomal pyroglutamyl aminopeptidase activity under basal and K+-stimulated conditions. Neurosci Lett 2000; 293: 199-202.

30. Canda A, Yu BH, Sze PY. Biochemical characterization of ethanol actions on dihydropyridine-sensitive Ca2+ channels in brain synaptosomes. Biochem Pharmacol 1995;50:1711-8.

31. Ramírez-Expósito MJ, Martínez-Martos JM, Mayas MD, Tsuboyama G, Prieto I, Aréchaga G, et al. Aminoglycoside antibiots neomycin and kanamycin inhibit the increase of pyroglutamyl aminopeptidase activity by depolarizing synaptosomes of frontal cortex of the rat. Rev Neurol 2000; 30: 1022-6.

32. Skoog I. A review on blood pressure and ischaemic shite matter lesions. Dement Geriatr Cogn Disord 1998; 9: 113-19.

33. Hohle S, Spitznagel H, Rascher W, Culman J, Unger T. Angiotensin AT1 receptor mediated vasopressin release and drinking are potentiated by an AT2 receptor antagonist. Eur J Pharmacol 1995; 275: 277-82.

34. Zini S, Furnie-Zaluski MC, Chauvel E, Roques BP, Corvol P, Llorens-Cortes C. Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: Predominant role of angiotensin III in the control of vasopressin release. Proc Natl Acad Sci 1996; 93: 11968-73.

35. Saavedra JM. Brain and pituitary angiotensin. Endocr Rev 1992; 13: 329-80.

36. Wright JW, Harding JW. Important role for angiotensin III and IV in the brain rein-angiotensin system. Brain Res Rev 1997; 25: 96-124.

37. Renaud LP, Bourque CW. Neurophysiology and neuropharmacology of hypothalamic magnocellular neurons secreting vasopressin and oxytocin. Prog Neurobiol 1991; 36: 131-69.

38. Song L, Wilk S, Healy DP. Aminopeptidase A antiserum inhibits intracerebroventricular angiotensin II induced dipsogenic and pressor responses. Brain Res 1997; 744: 1-6.

39. Chansel D, Czekalski S, Vandermeersch S, Buffet E, Fournie- Zaluski MC, Ardaillou R. Characterization of angiotensin IV degrading enzymes and receptors on rat mesangial cells. Am J Physiol 1998; 275: 535-42.

40. Ferrario CM, Chappell MC, Tallant EA, Brosnihan KB, Diz DI. Counterregulatory actions of angiotensin (1-7). Hypertension 1997; 30: 535-41.

41. Mungall BA, Shinkel TA, Sernia C. Inmunocytochemical localization of angiotensinogen in the fetal and neonatal rat brain. Neuroscien 1995; 67: 505-24.