Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 May;118(2):237–242. doi: 10.1111/j.1476-5381.1996.tb15393.x

Reversal by NPY, PYY and 3-36 molecular forms of NPY and PYY of intracisternal CRF-induced inhibition of gastric acid secretion in rats.

M Gué 1, J L Junien 1, J R Reeve Jr 1, J Rivier 1, D Grandt 1, Y Taché 1
PMCID: PMC1909620  PMID: 8735621

Abstract

1. The Y receptor subtype involved in the antagonism by neuropeptide Y (NPY) of intracisternal corticotropin-releasing factor (CRF)-induced inhibition of gastric acid secretion was studied in urethane-anaesthetized rats by use of peptides with various selectivity for Y1, Y2 and Y3 subtypes: NPY, a Y1, Y2 and Y3 agonist, peptide YY (PYY), a Y1 and Y2 agonist, [Leu31, Pro34]-NPY, a Y1 and Y3 agonist, NPY(3-36) and PYY(3-36), highly selective Y2 agonists and NPY(13-36) a weak Y2 and Y3 agonist. Peptides were injected intracisternally 10 min before intracisternal injection of CRF (10 micrograms) and gastric acid secretion was measured by the flushed technique for 1 h before and 2 h after pentagastrin-(10 micrograms kg-1 h-1, i.v.) infusion which started 10 min after CRF injection. 2. Intracisternal injection of CRF (10 micrograms) inhibited by 56% gastric acid secretion stimulated by pentagastrin. Intracisternal injection of NPY and PYY (0.1-0.5 microgram) did not influence the acid response to pentagastrin but blocked CRF-induced inhibition of pentagastrin-stimulated acid secretion. NPY(3-36) (0.5 microgram) and PYY(3-36) (0.25 and 0.5 microgram) also completely blocked the inhibitory action of CRF on pentagastrin-stimulated acid secretion. 3. [Leu31, Pro34]-NPY (0.5-5 micrograms) and NPY(13-36) (0.5-5 micrograms) injected intracisternally did not modify gastric acid secretion induced by pentagastrin or CRF inhibitory action. 4. The sigma antagonist, BMY 14802 (1 mg kg-1, s.c.) did not influence the acid response to pentagastrin but prevented the antagonism by PYY(3-36) (0.5 microgram) of the CRF antisecretory effect. 5. These results show that both PYY and NPY and the 3-36 forms of PYY and NPY are equipotent in blocking central CRF-induced inhibition of pentagastrin-stimulated gastric acid secretion. The structure-activity profile suggests a mediation through Y2 receptor subtype and the involvement of sigma binding sites.

Full text

PDF
237

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aicher S. A., Springston M., Berger S. B., Reis D. J., Wahlestedt C. Receptor-selective analogs demonstrate NPY/PYY receptor heterogeneity in rat brain. Neurosci Lett. 1991 Sep 2;130(1):32–36. doi: 10.1016/0304-3940(91)90220-n. [DOI] [PubMed] [Google Scholar]
  2. Bouchard P., Dumont Y., Fournier A., St-Pierre S., Quirion R. Evidence for in vivo interactions between neuropeptide Y-related peptides and sigma receptors in the mouse hippocampal formation. J Neurosci. 1993 Sep;13(9):3926–3931. doi: 10.1523/JNEUROSCI.13-09-03926.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dumont Y., Cadieux A., Pheng L. H., Fournier A., St-Pierre S., Quirion R. Peptide YY derivatives as selective neuropeptide Y/peptide YY Y1 and Y2 agonists devoided of activity for the Y3 receptor sub-type. Brain Res Mol Brain Res. 1994 Oct;26(1-2):320–324. doi: 10.1016/0169-328x(94)90105-8. [DOI] [PubMed] [Google Scholar]
  4. Dumont Y., Fournier A., St-Pierre S., Quirion R. Characterization of neuropeptide Y binding sites in rat brain membrane preparations using [125I][Leu31,Pro34]peptide YY and [125I]peptide YY3-36 as selective Y1 and Y2 radioligands. J Pharmacol Exp Ther. 1995 Feb;272(2):673–680. [PubMed] [Google Scholar]
  5. Dumont Y., Fournier A., St-Pierre S., Quirion R. Comparative characterization and autoradiographic distribution of neuropeptide Y receptor subtypes in the rat brain. J Neurosci. 1993 Jan;13(1):73–86. doi: 10.1523/JNEUROSCI.13-01-00073.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ergene E., Dunbar J. C., Barraco R. A. Visceroendocrine responses elicited by neuropeptide Y in the nucleus tractus solitarius. Brain Res Bull. 1993;32(5):461–465. doi: 10.1016/0361-9230(93)90291-i. [DOI] [PubMed] [Google Scholar]
  7. Fuhlendorff J., Gether U., Aakerlund L., Langeland-Johansen N., Thøgersen H., Melberg S. G., Olsen U. B., Thastrup O., Schwartz T. W. [Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist. Proc Natl Acad Sci U S A. 1990 Jan;87(1):182–186. doi: 10.1073/pnas.87.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gehlert D. R. Subtypes of receptors for neuropeptide Y: implications for the targeting of therapeutics. Life Sci. 1994;55(8):551–562. doi: 10.1016/0024-3205(94)00481-1. [DOI] [PubMed] [Google Scholar]
  9. Grandt D., Schimiczek M., Beglinger C., Layer P., Goebell H., Eysselein V. E., Reeve J. R., Jr Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept. 1994 May 5;51(2):151–159. doi: 10.1016/0167-0115(94)90204-6. [DOI] [PubMed] [Google Scholar]
  10. Grandt D., Schimiczek M., Struk K., Shively J., Eysselein V. E., Goebell H., Reeve J. R., Jr Characterization of two forms of peptide YY, PYY(1-36) and PYY(3-36), in the rabbit. Peptides. 1994;15(5):815–820. doi: 10.1016/0196-9781(94)90035-3. [DOI] [PubMed] [Google Scholar]
  11. Grandt D., Teyssen S., Schimiczek M., Reeve J. R., Jr, Feth F., Rascher W., Hirche H., Singer M. V., Layer P., Goebell H. Novel generation of hormone receptor specificity by amino terminal processing of peptide YY. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1299–1306. doi: 10.1016/s0006-291x(05)81547-5. [DOI] [PubMed] [Google Scholar]
  12. Grundemar L., Wahlestedt C., Reis D. J. Neuropeptide Y acts at an atypical receptor to evoke cardiovascular depression and to inhibit glutamate responsiveness in the brainstem. J Pharmacol Exp Ther. 1991 Aug;258(2):633–638. [PubMed] [Google Scholar]
  13. Gue M., Junien J. L., Del Rio C., Bueno L. Neuropeptide Y and sigma ligand (JO 1784) suppress stress-induced colonic motor disturbances in rats through sigma and cholecystokinin receptors. J Pharmacol Exp Ther. 1992 Jun;261(3):850–855. [PubMed] [Google Scholar]
  14. Gunion M. W., Taché Y. Intrahypothalamic microinfusion of corticotropin-releasing factor inhibits gastric acid secretion but increases secretion volume in rats. Brain Res. 1987 May 12;411(1):156–161. doi: 10.1016/0006-8993(87)90693-7. [DOI] [PubMed] [Google Scholar]
  15. Gué M., Yoneda M., Mönnikes H., Junien J. L., Taché Y. Central neuropeptide Y and the sigma ligand, JO 1784, reverse corticotropin-releasing factor-induced inhibition of gastric acid secretion in rats. Br J Pharmacol. 1992 Nov;107(3):642–647. doi: 10.1111/j.1476-5381.1992.tb14500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hernandez E. J., Whitcomb D. C., Vigna S. R., Taylor I. L. Saturable binding of circulating peptide YY in the dorsal vagal complex of rats. Am J Physiol. 1994 Mar;266(3 Pt 1):G511–G516. doi: 10.1152/ajpgi.1994.266.3.G511. [DOI] [PubMed] [Google Scholar]
  17. Heymann-Mönnikes I., Taché Y., Trauner M., Weiner H., Garrick T. CRF microinjected into the dorsal vagal complex inhibits TRH analog- and kainic acid-stimulated gastric contractility in rats. Brain Res. 1991 Jul 19;554(1-2):139–144. doi: 10.1016/0006-8993(91)90181-t. [DOI] [PubMed] [Google Scholar]
  18. Jiménez M., Buéno L. Inhibitory effects of neuropeptide Y (NPY) on CRF and stress-induced cecal motor response in rats. Life Sci. 1990;47(3):205–211. doi: 10.1016/0024-3205(90)90321-h. [DOI] [PubMed] [Google Scholar]
  19. Junien J. L., Gue M., Bueno L. Neuropeptide Y and sigma ligand (JO 1784) act through a Gi protein to block the psychological stress and corticotropin-releasing factor-induced colonic motor activation in rats. Neuropharmacology. 1991 Oct;30(10):1119–1124. doi: 10.1016/0028-3908(91)90142-x. [DOI] [PubMed] [Google Scholar]
  20. Larsen P. J., Sheikh S. P., Jakobsen C. R., Schwartz T. W., Mikkelsen J. D. Regional distribution of putative NPY Y1 receptors and neurons expressing Y1 mRNA in forebrain areas of the rat central nervous system. Eur J Neurosci. 1993 Dec 1;5(12):1622–1637. doi: 10.1111/j.1460-9568.1993.tb00231.x. [DOI] [PubMed] [Google Scholar]
  21. Leslie R. A., McDonald T. J., Robertson H. A. Autoradiographic localization of peptide YY and neuropeptide Y binding sites in the medulla oblongata. Peptides. 1988 Sep-Oct;9(5):1071–1076. doi: 10.1016/0196-9781(88)90091-5. [DOI] [PubMed] [Google Scholar]
  22. Matsuda M., Aono M., Moriga M., Okuma M. Centrally administered NPY stimulated gastric acid and pepsin secretion by a vagally mediated mechanism. Regul Pept. 1991 Jul 23;35(1):31–41. doi: 10.1016/0167-0115(91)90251-b. [DOI] [PubMed] [Google Scholar]
  23. Monnet F. P., Debonnel G., Fournier A., de Montigny C. Neuropeptide Y potentiates the N-methyl-D-aspartate response in the CA3 dorsal hippocampus. II. Involvement of a subtype of sigma receptor. J Pharmacol Exp Ther. 1992 Dec;263(3):1219–1225. [PubMed] [Google Scholar]
  24. Nakajima T., Yashima Y., Nakamura K. Quantitative autoradiographic localization of neuropeptide Y receptors in the rat lower brainstem. Brain Res. 1986 Aug 13;380(1):144–150. doi: 10.1016/0006-8993(86)91438-1. [DOI] [PubMed] [Google Scholar]
  25. Reymond M. T., Delmas L., Koerber S. C., Brown M. R., Rivier J. E. Truncated, branched, and/or cyclic analogues of neuropeptide Y: importance of the pancreatic peptide fold in the design of specific Y2 receptor ligands. J Med Chem. 1992 Oct 2;35(20):3653–3659. doi: 10.1021/jm00098a009. [DOI] [PubMed] [Google Scholar]
  26. Sheikh S. P., Håkanson R., Schwartz T. W. Y1 and Y2 receptors for neuropeptide Y. FEBS Lett. 1989 Mar 13;245(1-2):209–214. doi: 10.1016/0014-5793(89)80223-6. [DOI] [PubMed] [Google Scholar]
  27. Su T. P., Schell S. E., Ford-Rice F. Y., London E. D. Correlation of inhibitory potencies of putative antagonists for sigma receptors in brain and spleen. Eur J Pharmacol. 1988 Apr 13;148(3):467–470. doi: 10.1016/0014-2999(88)90130-6. [DOI] [PubMed] [Google Scholar]
  28. Taché Y., Goto Y., Gunion M. W., Vale W., River J., Brown M. Inhibition of gastric acid secretion in rats by intracerebral injection of corticotropin-releasing factor. Science. 1983 Nov 25;222(4626):935–937. doi: 10.1126/science.6415815. [DOI] [PubMed] [Google Scholar]
  29. Walker J. M., Bowen W. D., Walker F. O., Matsumoto R. R., De Costa B., Rice K. C. Sigma receptors: biology and function. Pharmacol Rev. 1990 Dec;42(4):355–402. [PubMed] [Google Scholar]
  30. Wan C. P., Lau B. H. Neuropeptide Y receptor subtypes. Life Sci. 1995 Feb 17;56(13):1055–1064. doi: 10.1016/0024-3205(95)00041-4. [DOI] [PubMed] [Google Scholar]
  31. Yang H., Taché Y. PYY in brain stem nuclei induces vagal stimulation of gastric acid secretion in rats. Am J Physiol. 1995 Jun;268(6 Pt 1):G943–G948. doi: 10.1152/ajpgi.1995.268.6.G943. [DOI] [PubMed] [Google Scholar]
  32. Yoneda M., Junien J. L., Taché Y. Central action of sigma receptor ligand, JO 1784, to suppress CRF-induced inhibition of gastric function in conscious rats. Eur J Pharmacol. 1992 Nov 17;223(2-3):197–199. doi: 10.1016/0014-2999(92)94840-r. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES