Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Oct;116(4):2274–2278. doi: 10.1111/j.1476-5381.1995.tb15064.x

Mediation by CCKB receptors of the CCK-evoked hyperaemia in rat gastric mucosa.

A Heinemann 1, M Jocic 1, U Holzer-Petsche 1, G Pethö 1, B M Peskar 1, D C Horwell 1, P Holzer 1
PMCID: PMC1908968  PMID: 8564259

Abstract

1. Cholecystokinin octapeptide (CCK-8) and gastrin-17 augment gastric mucosal blood flow in the rat. The present study examined whether the gastric vasodilator effect of these peptides is mediated by CCKA or CCKB receptors. 2. Intravenous injection of CAM-1481 (1 mg kg-1), a dipeptoid antagonist of CCKA receptors, or CAM-1028, a dipeptoid CCKB receptor antagonist (1 mg kg-1), had no effect on basal gastric mucosal blood flow as determined by the clearance of hydrogen in urethane-anaesthetized rats. 3. Intravenous infusion of CCK-8 or gastrin-17 (8-200 pmol min-1) increased gastric mucosal blood flow in a dose-dependent fashion. The CCKB receptor antagonist, CAM-1028, significantly attenuated the hyperaemic response to CCK-8 and gastrin-17 whereas the CCKA receptor antagonist, CAM-1481, did not antagonize CCK-8 but caused a slight attenuation of the vasodilator response to gastrin-17. 4. The selectivity of the two antagonists was proved by the findings that CAM-1028, but not CAM-1481, inhibited gastric acid secretion evoked by CCK-8 or gastrin-17 (CCKB receptor assay) while CAM-1481, but not CAM-1028, inhibited the CCK-8-induced contraction of guinea-pig isolated gall bladder strips (CCKA receptor assay). 5. These data show that the actions of CCK-8 and gastrin-17 to increase mucosal blood flow in the rat stomach are primarily mediated by CCKB receptors.

Full text

PDF
2274

Selected References

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

  1. Bishop L. A., Gerskowitch V. P., Hull R. A., Shankley N. P., Black J. W. Combined dose-ratio analysis of cholecystokinin receptor antagonists, devazepide, lorglumide and loxiglumide in the guinea-pig gall bladder. Br J Pharmacol. 1992 May;106(1):61–66. doi: 10.1111/j.1476-5381.1992.tb14293.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boden P. R., Higginbottom M., Hill D. R., Horwell D. C., Hughes J., Rees D. C., Roberts E., Singh L., Suman-Chauhan N., Woodruff G. N. Cholecystokinin dipeptoid antagonists: design, synthesis, and anxiolytic profile of some novel CCK-A and CCK-B selective and "mixed" CCK-A/CCK-B antagonists. J Med Chem. 1993 Mar 5;36(5):552–565. doi: 10.1021/jm00057a005. [DOI] [PubMed] [Google Scholar]
  3. Bowen J. C., Pawlik W., Fang W. F., Jacobson E. D. Pharmacologic effects of gastrointestinal hormones on intestinal oxygen consumption and blood flow. Surgery. 1975 Oct;78(4):515–519. [PubMed] [Google Scholar]
  4. Chou C. C., Hsieh C. P., Dabney J. M. Comparison of vascular effects of gastrointestinal hormones on various organs. Am J Physiol. 1977 Feb;232(2):H103–H109. doi: 10.1152/ajpheart.1977.232.2.H103. [DOI] [PubMed] [Google Scholar]
  5. Corp E. S., McQuade J., Moran T. H., Smith G. P. Characterization of type A and type B CCK receptor binding sites in rat vagus nerve. Brain Res. 1993 Sep 24;623(1):161–166. doi: 10.1016/0006-8993(93)90024-h. [DOI] [PubMed] [Google Scholar]
  6. Evangelista S., Maggi C. A. Protection induced by cholecystokinin-8 (CCK-8) in ethanol-induced gastric lesions is mediated via vagal capsaicin-sensitive fibres and CCKA receptors. Br J Pharmacol. 1991 Jan;102(1):119–122. doi: 10.1111/j.1476-5381.1991.tb12142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fara J. W., Madden K. S. Effect of secretin and cholecystokinin on small intestinal blood flow distribution. Am J Physiol. 1975 Nov;229(5):1365–1370. doi: 10.1152/ajplegacy.1975.229.5.1365. [DOI] [PubMed] [Google Scholar]
  8. Forster E. R., Green T., Elliot M., Bremner A., Dockray G. J. Gastric emptying in rats: role of afferent neurons and cholecystokinin. Am J Physiol. 1990 Apr;258(4 Pt 1):G552–G556. doi: 10.1152/ajpgi.1990.258.4.G552. [DOI] [PubMed] [Google Scholar]
  9. Gully D., Fréhel D., Marcy C., Spinazzé A., Lespy L., Neliat G., Maffrand J. P., Le Fur G. Peripheral biological activity of SR 27897: a new potent non-peptide antagonist of CCKA receptors. Eur J Pharmacol. 1993 Feb 23;232(1):13–19. doi: 10.1016/0014-2999(93)90722-t. [DOI] [PubMed] [Google Scholar]
  10. Guth P. H., Smith E. The effect of gastrointestinal hormones on the gastric microcirculation. Gastroenterology. 1976 Sep;71(3):435–438. [PubMed] [Google Scholar]
  11. Holzer P., Livingston E. H., Guth P. H. Sensory neurons signal for an increase in rat gastric mucosal blood flow in the face of pending acid injury. Gastroenterology. 1991 Aug;101(2):416–423. doi: 10.1016/0016-5085(91)90020-l. [DOI] [PubMed] [Google Scholar]
  12. Hughes J., Boden P., Costall B., Domeney A., Kelly E., Horwell D. C., Hunter J. C., Pinnock R. D., Woodruff G. N. Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6728–6732. doi: 10.1073/pnas.87.17.6728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Janssen P. J., Gardiner S. M., Compton A. M., Bennett T. Mechanisms contributing to the differential haemodynamic effects of bombesin and cholecystokinin in conscious, Long Evans rats. Br J Pharmacol. 1991 Jan;102(1):123–134. doi: 10.1111/j.1476-5381.1991.tb12143.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leung F. W., Guth P. H., Scremin O. U., Golanska E. M., Kauffman G. L., Jr Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit. Gastroenterology. 1984 Jul;87(1):28–36. [PubMed] [Google Scholar]
  15. Lin C. W., Miller T. R. Both CCK-A and CCK-B/gastrin receptors are present on rabbit vagus nerve. Am J Physiol. 1992 Sep;263(3 Pt 2):R591–R595. doi: 10.1152/ajpregu.1992.263.3.R591. [DOI] [PubMed] [Google Scholar]
  16. Livingston E. H., Reedy T., Leung F. W., Guth P. H. Computerized curve fitting in the analysis of hydrogen gas clearance curves. Am J Physiol. 1989 Oct;257(4 Pt 1):G668–G675. doi: 10.1152/ajpgi.1989.257.4.G668. [DOI] [PubMed] [Google Scholar]
  17. Lloyd K. C., Raybould H. E., Walsh J. H. Cholecystokinin inhibits gastric acid secretion through type "A" cholecystokinin receptors and somatostatin in rats. Am J Physiol. 1992 Sep;263(3 Pt 1):G287–G292. doi: 10.1152/ajpgi.1992.263.3.G287. [DOI] [PubMed] [Google Scholar]
  18. Prinz C., Kajimura M., Scott D. R., Mercier F., Helander H. F., Sachs G. Histamine secretion from rat enterochromaffinlike cells. Gastroenterology. 1993 Aug;105(2):449–461. doi: 10.1016/0016-5085(93)90719-s. [DOI] [PubMed] [Google Scholar]
  19. Richardson P. D., Withrington P. G. The effects of glucagon, secretin, pancreozymin and pentagastrin on the hepatic arterial vascular bed of the dog. Br J Pharmacol. 1977 Jan;59(1):147–156. doi: 10.1111/j.1476-5381.1977.tb06989.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES