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. 1995 Oct 15;488(Pt 2):501–508. doi: 10.1113/jphysiol.1995.sp020984

The mechanism of inhibitory action of secretin on gastric acid secretion in conscious rats.

K Shimizu 1, P Li 1, K Y Lee 1, T M Chang 1, W Y Chey 1
PMCID: PMC1156688  PMID: 8568688

Abstract

1. Secretin has been recognized as an important enterogastrone. In order to investigate the mechanism of secretin-induced inhibition of gastric acid secretion, the effects of both anti-somatostatin antibody and indomethacin on acid secretion were examined in conscious rats with gastric cannulas. 2. Secretin given intravenously at 5.6 pmol kg-1 h-1 inhibited profoundly the acid secretion stimulated by pentagastrin at 0.3 microgram kg-1 h-1. 3. When a rabbit antisomatostatin serum was given intravenously, it not only abolished the secretin-induced inhibition on the pentagastrin-stimulated acid secretion, but also augmented both basal and pentagastrin-stimulated acid secretion. 4. Indomethacin also significantly augmented basal acid secretion, starting 45 min after the drug delivery began. It reversed the secretin-induced inhibition but it did not augment the pentagastrin-stimulated acid secretion. 5. Neither antisomatostatin serum influenced prostaglandin E2-induced inhibition of the pentagastrin-stimulated acid secretion, nor did indomethacin affect the inhibition by somatostatin, suggesting strongly that the inhibition by somatostatin is not mediated by endogenous prostaglandins, nor is that by prostaglandins E2 mediated by endogenous somatostatin. 6. It is concluded that the inhibitory action of secretin on pentagastrin-stimulated gastric acid secretion is mediated by both somatostatin and prostaglandins in conscious rats. The two inhibitors do not seem to interact endogenously for the inhibition of acid secretion. While endogenous somatostatin exerts a tonic inhibitory effect on both basal and pentagastrin-simulated acid secretion, prostaglandins augment basal acid secretion only.

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Selected References

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  1. Albinus M., Gomez-Pan A., Hirst B. H., Shaw B. Evidence against prostaglandin-mediation of somatostatin-inhibition of gastric secretions. Regul Pept. 1985 Mar;10(2-3):259–266. doi: 10.1016/0167-0115(85)90020-5. [DOI] [PubMed] [Google Scholar]
  2. Bloom S. R., Mortimer C. H., Thorner M. O., Besser G. M., Hall R., Gomez-Pan A., Roy V. M., Russell R. C., Coy D. H., Kastin A. J. Inhibition of gastrin and gastric-acid secretion by growth-hormone release-inhibiting hormone. Lancet. 1974 Nov 9;2(7889):1106–1109. doi: 10.1016/s0140-6736(74)90869-1. [DOI] [PubMed] [Google Scholar]
  3. Buchan A. M., Meloche R. M., Kwok Y. N., Kofod H. Effect of cholecystokinin and secretin on somatostatin release from cultured antral cells. Gastroenterology. 1993 May;104(5):1414–1419. doi: 10.1016/0016-5085(93)90350-l. [DOI] [PubMed] [Google Scholar]
  4. Chey W. Y., Sivasomboon B., Hendricks J. Actions and interactions of gut hormones and histamine on gastric secretion of acid in the rat. Am J Physiol. 1973 Apr;224(4):852–856. doi: 10.1152/ajplegacy.1973.224.4.852. [DOI] [PubMed] [Google Scholar]
  5. Chiba T., Taminato T., Kadowaki S., Abe H., Chihara K., Seino Y., Matsukura S., Fujita T. Effects of glucagon, secretin, and vasoactive intestinal polypeptide on gastric somatostatin and gastrin release from isolated perfused rat stomach. Gastroenterology. 1980 Jul;79(1):67–71. [PubMed] [Google Scholar]
  6. Christiansen J., Hansen B., Hilsted L., Schaffalitzky de Muckadell O. B. Effect of low-dose exogenous secretin on pentagastrin- and meal-stimulated gastric acid secretion in humans. Dig Dis Sci. 1988 Oct;33(10):1277–1281. doi: 10.1007/BF01536680. [DOI] [PubMed] [Google Scholar]
  7. Chung I., Li P., Lee K., Chang T., Chey W. Y. Dual inhibitory mechanism of secretin action on acid secretion in totally isolated, vascularly perfused rat stomach. Gastroenterology. 1994 Dec;107(6):1751–1758. doi: 10.1016/0016-5085(94)90817-6. [DOI] [PubMed] [Google Scholar]
  8. Coy D. H., Coy E. J., Lee K. Y., Chey W. Y. Solid-phase synthesis and biological activities of gastrointestinal hormones: secretin and motilin. Peptides. 1982 Mar-Apr;3(2):137–141. doi: 10.1016/0196-9781(82)90042-0. [DOI] [PubMed] [Google Scholar]
  9. Harty R. F., Maico D. G., McGuigan J. E. Somatostatin inhibition of basal and carbachol-stimulated gastrin release in rat antral organ culture. Gastroenterology. 1981 Oct;81(4):707–712. [PubMed] [Google Scholar]
  10. Hayes J. R., Johnson D. G., Koerker D., Williams R. H. Inhibition of gastrin release by somatosatin in vitro. Endocrinology. 1975 Jun;96(6):1374–1376. doi: 10.1210/endo-96-6-1374. [DOI] [PubMed] [Google Scholar]
  11. Jin H. O., Lee K. Y., Chang T. M., Chey W. Y., Dubois A. Secretin: a physiological regulator of gastric emptying and acid output in dogs. Am J Physiol. 1994 Oct;267(4 Pt 1):G702–G708. doi: 10.1152/ajpgi.1994.267.4.G702. [DOI] [PubMed] [Google Scholar]
  12. Larsson L. I., Goltermann N., de Magistris L., Rehfeld J. F., Schwartz T. W. Somatostatin cell processes as pathways for paracrine secretion. Science. 1979 Sep 28;205(4413):1393–1395. doi: 10.1126/science.382360. [DOI] [PubMed] [Google Scholar]
  13. Lee K. Y., Lee Y. L., Kim C. D., Chang T. M., Chey W. Y. Mechanism of action of insulin on pancreatic exocrine secretion in perfused rat pancreas. Am J Physiol. 1994 Aug;267(2 Pt 1):G207–G212. doi: 10.1152/ajpgi.1994.267.2.G207. [DOI] [PubMed] [Google Scholar]
  14. Lee K. Y., Zhou L., Ren X. S., Chang T. M., Chey W. Y. An important role of endogenous insulin on exocrine pancreatic secretion in rats. Am J Physiol. 1990 Feb;258(2 Pt 1):G268–G274. doi: 10.1152/ajpgi.1990.258.2.G268. [DOI] [PubMed] [Google Scholar]
  15. Ligumsky M., Goto Y., Debas H., Yamada T. Prostaglandins mediate inhibition of gastric acid secretion by somatostatin in the rat. Science. 1983 Jan 21;219(4582):301–303. doi: 10.1126/science.6129701. [DOI] [PubMed] [Google Scholar]
  16. MacLellan D. G., Upp J. R., Jr, Thompson J. C. Influence of endogenous prostaglandins on secretin-mediated inhibition of gastric acid secretion in dogs. Gastroenterology. 1988 Sep;95(3):625–629. doi: 10.1016/s0016-5085(88)80007-6. [DOI] [PubMed] [Google Scholar]
  17. Mogard M. H., Kauffman G. L., Jr, Pehlevanian M., Golanska E., Elashoff J. D., Walsh J. H. Prostaglandins may not mediate inhibition of gastric acid secretion by somatostatin in the rat. Regul Pept. 1985 Mar;10(2-3):231–236. doi: 10.1016/0167-0115(85)90017-5. [DOI] [PubMed] [Google Scholar]
  18. Park J., Chiba T., Yamada T. Mechanisms for direct inhibition of canine gastric parietal cells by somatostatin. J Biol Chem. 1987 Oct 15;262(29):14190–14196. [PubMed] [Google Scholar]
  19. Rhee J. C., Chang T. M., Lee K. Y., Jo Y. H., Chey W. Y. Mechanism of oleic acid-induced inhibition on gastric acid secretion in rats. Am J Physiol. 1991 Apr;260(4 Pt 1):G564–G570. doi: 10.1152/ajpgi.1991.260.4.G564. [DOI] [PubMed] [Google Scholar]
  20. Schepp W., Chan C. B., Giraud A. S., Avedian D., Chen M. C., Chew P., Walsh J. H., Soll A. H. Effects of prostaglandins on gastrin release from canine antral mucosal cells in primary culture. Am J Physiol. 1994 Feb;266(2 Pt 1):G194–G200. doi: 10.1152/ajpgi.1994.266.2.G194. [DOI] [PubMed] [Google Scholar]
  21. Schubert M. L., Edwards N. F., Arimura A., Makhlouf G. M. Paracrine regulation of gastric acid secretion by fundic somatostatin. Am J Physiol. 1987 Apr;252(4 Pt 1):G485–G490. doi: 10.1152/ajpgi.1987.252.4.G485. [DOI] [PubMed] [Google Scholar]
  22. Seal A. M., Meloche R. M., Liu Y. Q., Buchan A. M., Brown J. C. Effects of monoclonal antibodies to somatostatin on somatostatin-induced and intestinal fat-induced inhibition of gastric acid secretion in the rat. Gastroenterology. 1987 May;92(5 Pt 1):1187–1192. doi: 10.1016/s0016-5085(87)91076-6. [DOI] [PubMed] [Google Scholar]
  23. Shiratori K., Watanabe S., Takeuchi T. Role of endogenous prostaglandins in secretin- and plaunotol-induced inhibition of gastric acid secretion in the rat. Am J Gastroenterol. 1993 Jan;88(1):84–89. [PubMed] [Google Scholar]
  24. Shiratori K., Watanabe S., Takeuchi T. Role of endogenous secretin and cholecystokinin in intraduodenal oleic acid-induced inhibition of gastric acid secretion in rats. Dig Dis Sci. 1992 Mar;37(3):397–402. doi: 10.1007/BF01307734. [DOI] [PubMed] [Google Scholar]
  25. Short G. M., Doyle J. W., Wolfe M. M. Effect of antibodies to somatostatin on acid secretion and gastrin release by the isolated perfused rat stomach. Gastroenterology. 1985 Apr;88(4):984–988. doi: 10.1016/s0016-5085(85)80018-4. [DOI] [PubMed] [Google Scholar]
  26. Sugano K., Park J., Soll A. H., Yamada T. Stimulation of gastrin release by bombesin and canine gastrin-releasing peptides. Studies with isolated canine G cells in primary culture. J Clin Invest. 1987 Mar;79(3):935–942. doi: 10.1172/JCI112904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wolfe M. M., Jain D. K., Reel G. M., McGuigan J. E. Effects of carbachol on gastrin and somatostatin release in rat antral tissue culture. Gastroenterology. 1984 Jul;87(1):86–93. [PubMed] [Google Scholar]
  28. Wolfe M. M., Reel G. M., McGuigan J. E. Inhibition of gastrin release by secretin is mediated by somatostatin in cultured rat antral mucosa. J Clin Invest. 1983 Nov;72(5):1586–1593. doi: 10.1172/JCI111117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yang H., Wong H., Wu V., Walsh J. H., Taché Y. Somatostatin monoclonal antibody immunoneutralization increases gastrin and gastric acid secretion in urethane-anesthetized rats. Gastroenterology. 1990 Sep;99(3):659–665. doi: 10.1016/0016-5085(90)90952-w. [DOI] [PubMed] [Google Scholar]
  30. You C. H., Chey W. Y. Secretin is an enterogastrone in humans. Dig Dis Sci. 1987 May;32(5):466–471. doi: 10.1007/BF01296028. [DOI] [PubMed] [Google Scholar]

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