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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Dec;89(4):627–633. doi: 10.1111/j.1476-5381.1986.tb11166.x

Effects of calcium channel blockers on gastric emptying and acid secretion of the rat in vivo.

R Brage, J Cortijo, J Esplugues, J V Esplugues, E Martí-Bonmatí, C Rodriguez
PMCID: PMC1917224  PMID: 3814903

Abstract

Experiments were designed to evaluate the effects of three calcium channel blockers (verapamil, diltiazem and cinnarizine) on gastric emptying and secretion in the rat. Pretreatment with the calcium blockers delayed gastric emptying of phenol red in a dose-dependent manner. Verapamil was the most effective of the agents tested. Verapamil and diltiazem inhibited gastric acid secretion in the pylorus-ligated rat without affecting pepsin output. Cinnarizine was ineffective in this model. When the perfused lumen of the anaesthetized rat was used, verapamil was found to inhibit responses to carbachol or histamine more than those to pentagastrin. Further, we found a greater sensitivity to verapamil for basal compared with vagal-stimulated (2-deoxy-D-glucose) acid secretion. Neither diltiazem nor cinnarizine modified gastric acid secretion in this experimental model. These findings are discussed in relation to the role of extracellular calcium in gastric motility and secretion, and the existence of a regional and functional selectivity for calcium blockers is proposed.

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Selected References

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  1. Aadland E., Berstad A. Effect of verapamil on gastric secretion in man. Scand J Gastroenterol. 1983 Oct;18(7):969–971. doi: 10.3109/00365528309182124. [DOI] [PubMed] [Google Scholar]
  2. Baumgartner A., Drack E., Halter F., Scheurer U. Effects of pinaverium bromide and verapamil on the motility of the rat isolated colon. Br J Pharmacol. 1985 Sep;86(1):89–94. doi: 10.1111/j.1476-5381.1985.tb09438.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berglindh T., Sachs G., Takeguchi N. Ca2+-dependent secretagogue stimulation in isolated rabbit gastric glands. Am J Physiol. 1980 Aug;239(2):G90–G94. doi: 10.1152/ajpgi.1980.239.2.G90. [DOI] [PubMed] [Google Scholar]
  4. Bunce K. T., Honey A. C., Parsons M. E. Investigation of the role of extracellular calcium in the control of acid secretion in the isolated whole stomach of the rat. Br J Pharmacol. 1979 Sep;67(1):123–131. [PMC free article] [PubMed] [Google Scholar]
  5. Castell D. O. Calcium-channel blocking agents for gastrointestinal disorders. Am J Cardiol. 1985 Jan 25;55(3):210B–213B. doi: 10.1016/0002-9149(85)90633-2. [DOI] [PubMed] [Google Scholar]
  6. Curtis M. J., MacLeod B. A., Walker M. J. Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat. Br J Pharmacol. 1984 Oct;83(2):373–385. doi: 10.1111/j.1476-5381.1984.tb16497.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Esplugues J. V., Bulbena O., Escolar G., Martí-Bonmatí E., Esplugues J. Effects of zinc acexamate on gastric mucosal resistance factors. Eur J Pharmacol. 1985 Feb 26;109(2):145–151. doi: 10.1016/0014-2999(85)90415-7. [DOI] [PubMed] [Google Scholar]
  8. Esplugues J., Lloris J. M., Martí-Bonmatí E., Morcillo E. J. Effects of beta-adrenoceptor drug stimulation on various models of gastric ulcer in rats. Br J Pharmacol. 1982 Aug;76(4):587–594. doi: 10.1111/j.1476-5381.1982.tb09258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GHOSH M. N., SCHILD H. O. Continuous recording of acid gastric secretion in the rat. Br J Pharmacol Chemother. 1958 Mar;13(1):54–61. doi: 10.1111/j.1476-5381.1958.tb00190.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goyal R. K., Rattan S. Effects of sodium nitroprusside and verapamil on lower esophageal sphincter. Am J Physiol. 1980 Jan;238(1):G40–G44. doi: 10.1152/ajpgi.1980.238.1.G40. [DOI] [PubMed] [Google Scholar]
  11. Hongo M., Traube M., McAllister R. G., Jr, McCallum R. W. Effects of nifedipine on esophageal motor function in humans: correlation with plasma nifedipine concentration. Gastroenterology. 1984 Jan;86(1):8–12. [PubMed] [Google Scholar]
  12. Im W. B., Blakeman D. P., Mendlein J., Sachs G. Inhibition of (H+ + K+)-ATPase and H+ accumulation in hog gastric membranes by trifluoperazine, verapamil and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate. Biochim Biophys Acta. 1984 Feb 29;770(1):65–72. doi: 10.1016/0005-2736(84)90074-9. [DOI] [PubMed] [Google Scholar]
  13. Ishikawa S., Komori K., Nagao T., Suzuki H. Effects of diltiazem on electrical responses evoked spontaneously or by electrical stimulation in the antrum smooth muscle cells of the guinea-pig stomach. Br J Pharmacol. 1985 Dec;86(4):789–797. doi: 10.1111/j.1476-5381.1985.tb11100.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kirkegaard P., Christiansen J., Petersen B., Skov Olsen P. Calcium and stimulus-secretion coupling in gastric fundic mucosa. Effect of inhibition of calcium transport by verapamil on gastric acid secretion in the isolated guinea pig fundic mucosa and in healthy subjects. Scand J Gastroenterol. 1982 Jun;17(4):533–538. doi: 10.3109/00365528209182245. [DOI] [PubMed] [Google Scholar]
  15. Levine R. A., Petokas S., Starr A., Eich R. H. Effect of verapamil on basal and pentagastrin-stimulated gastric acid secretion. Clin Pharmacol Ther. 1983 Sep;34(3):399–402. doi: 10.1038/clpt.1983.186. [DOI] [PubMed] [Google Scholar]
  16. Main I. H., Pearce J. B. Effects of calcium on acid secretion from the rat isolated gastric mucosa during stimulation with histamine, pentagastrin, methacholine and dibutyryl cyclic adenosine-3',5'-monophosphate. Br J Pharmacol. 1978 Nov;64(3):359–368. [PMC free article] [PubMed] [Google Scholar]
  17. Milledge J. S., Catley D. M., Blume F. D., West J. B. Renin, angiotensin-converting enzyme, and aldosterone in humans on Mount Everest. J Appl Physiol Respir Environ Exerc Physiol. 1983 Oct;55(4):1109–1112. doi: 10.1152/jappl.1983.55.4.1109. [DOI] [PubMed] [Google Scholar]
  18. Morales-Olivas F. J., Cortijo J., Esplugues J. V., Rubio E., Esplugues J. Effect of verapamil and diltiazem on isolated gastro-oesophageal sphincter of the rat. J Pharm Pharmacol. 1985 Mar;37(3):208–209. doi: 10.1111/j.2042-7158.1985.tb05044.x. [DOI] [PubMed] [Google Scholar]
  19. Ogle C. W., Cho C. H., Tong M. C., Koo M. W. The influence of verapamil on the gastric effects of stress in rats. Eur J Pharmacol. 1985 Jun 19;112(3):399–404. doi: 10.1016/0014-2999(85)90787-3. [DOI] [PubMed] [Google Scholar]
  20. Scarpignato C., Capovilla T., Bertaccini G. Action of caerulein on gastric emptying of the conscious rat. Arch Int Pharmacodyn Ther. 1980 Aug;246(2):286–294. [PubMed] [Google Scholar]
  21. Singh B. N., Baky S., Nademanee K. Second-generation calcium antagonists: search for greater selectivity and versatility. Am J Cardiol. 1985 Jan 25;55(3):214B–221B. doi: 10.1016/0002-9149(85)90634-4. [DOI] [PubMed] [Google Scholar]
  22. Soll A. H. Extracellular calcium and cholinergic stimulation of isolated canine parietal cells. J Clin Invest. 1981 Jul;68(1):270–278. doi: 10.1172/JCI110243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sonnenberg A., Meckel F., Eckhardt U., Scholten T. The effect of the calcium antagonist verapamil on gastric acid secretion in humans. Hepatogastroenterology. 1984 Apr;31(2):80–84. [PubMed] [Google Scholar]
  24. Spedding M. Activators and inactivators of Ca++ channels: new perspectives. J Pharmacol. 1985 Oct-Dec;16(4):319–343. [PubMed] [Google Scholar]
  25. Szelenyi I. Calcium, histamine, and pentagastrin: speculations about the regulation of gastric acid secretion at cellular level. Agents Actions. 1980 Apr;10(1 Pt 2):187–190. doi: 10.1007/BF02024209. [DOI] [PubMed] [Google Scholar]

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