Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1984 Oct;355:465–478. doi: 10.1113/jphysiol.1984.sp015432

The involvement of calcium in the intestinal response to secretagogues in the rat.

J Hardcastle, P T Hardcastle, J M Noble
PMCID: PMC1193504  PMID: 6092629

Abstract

The involvement of Ca2+ in the regulation of intestinal secretion was investigated in stripped sheets of rat mid-intestine. Removal of serosal Ca2+ together with the addition of EGTA at concentrations of 0.5 and 1 mM inhibited the rise in short-circuit current (s.c.c.) induced by both acetylcholine and theophylline, a similar degree of inhibition being observed with both secretagogues. Ca2+-free serosal fluid with 0.5 mM-EGTA added reduced significantly the rises in s.c.c. induced by A23187, acetylcholine, 5-hydroxytryptamine, theophylline, dibutyryl cyclic AMP and prostaglandin E2, but not the increased s.c.c. associated with glucose absorption. The Ca2+ channel blocker verapamil produced similar results. The calmodulin antagonist trifluoperazine inhibited secretagogue action while its sulphoxide derivative was without effect at the same concentration. The intracellular Ca2+ antagonist TMB-8 reduced the increased s.c.c. observed with acetylcholine and dibutyryl cyclic AMP. The net Cl- secretion, but not the decreased mucosal-to-serosal Na+ flux, induced by acetylcholine was abolished in Ca2+-free conditions. There was no consistent effect on the reduction in the residual ion flux caused by acetylcholine. Absence of Ca2+ converted the stimulation of Cl- secretion induced by dibutyryl cyclic AMP observed under control conditions to an enhancement of net Na+ and Cl- absorption. It is concluded that intestinal secretagogues, whether they act through cyclic AMP or not, require both internal and external sources of Ca2+ if they are to produce their full effects. Moreover, it appears that the nature of the response to dibutyryl cyclic AMP depends on the prevailing Ca2+ concentration.

Full text

PDF
476

Selected References

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

  1. Bolton J. E., Field M. Ca ionophore-stimulated ion secretion in rabbit ileal mucosa: relation to actions of cyclic 3',5'-AMP and carbamylcholine. J Membr Biol. 1977 Jun 30;35(2):159–173. doi: 10.1007/BF01869947. [DOI] [PubMed] [Google Scholar]
  2. Charo I. F., Feinman R. D., Detwiler T. C. Inhibition of platelet secretion by an antagonist of intracellular calcium. Biochem Biophys Res Commun. 1976 Oct 18;72(4):1462–1467. doi: 10.1016/s0006-291x(76)80178-7. [DOI] [PubMed] [Google Scholar]
  3. Corbett C. L., Isaacs P. E., Riley A. K., Turnberg L. A. Human intestinal ion transport in vitro. Gut. 1977 Feb;18(2):136–140. doi: 10.1136/gut.18.2.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Donowitz M., Asarkof N., Pike G. Calcium dependence of serotonin-induced changes in rabbit ileal electrolyte transport. J Clin Invest. 1980 Aug;66(2):341–352. doi: 10.1172/JCI109862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Donowitz M. Ca2+ in the control of active intestinal Na and Cl transport: involvement in neurohumoral action. Am J Physiol. 1983 Aug;245(2):G165–G177. doi: 10.1152/ajpgi.1983.245.2.G165. [DOI] [PubMed] [Google Scholar]
  6. Donowitz M., Fogel R., Battisti L., Asarkof N. The neurohumoral secretagogues carbachol, substance P and neurotensin increase Ca++ influx and calcium content in rabbit ileum. Life Sci. 1982 Nov 1;31(18):1929–1937. doi: 10.1016/0024-3205(82)90031-5. [DOI] [PubMed] [Google Scholar]
  7. Field M., Fromm D., McColl I. Ion transport in rabbit ileal mucosa. I. Na and Cl fluxes and short-circuit current. Am J Physiol. 1971 May;220(5):1388–1396. doi: 10.1152/ajplegacy.1971.220.5.1388. [DOI] [PubMed] [Google Scholar]
  8. Field M. Ion transport in rabbit ileal mucosa. II. Effects of cyclic 3', 5'-AMP. Am J Physiol. 1971 Oct;221(4):992–997. doi: 10.1152/ajplegacy.1971.221.4.992. [DOI] [PubMed] [Google Scholar]
  9. Frizzell R. A. Active chloride secretion by rabbit colon: calcium-dependent stimulation by ionophore A23187. J Membr Biol. 1977 Jun 30;35(2):175–187. doi: 10.1007/BF01869948. [DOI] [PubMed] [Google Scholar]
  10. Garcia R., Laychock S. G., Rubin R. P. Inhibition of dibutyryl cyclic AMP induced steroidogenesis in rat adrenocortical cells by the putative calcium antagonist TMB-8. J Steroid Biochem. 1982 Feb;16(2):317–322. doi: 10.1016/0022-4731(82)90183-2. [DOI] [PubMed] [Google Scholar]
  11. Hardcastle J., Hardcastle P. T., Noble J. M. The effect of barium chloride on intestinal secretion in the rat. J Physiol. 1983 Nov;344:69–80. doi: 10.1113/jphysiol.1983.sp014924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hardcastle J., Hardcastle P. T., Read N. W., Redfern J. S. The action of loperamide in inhibiting prostaglandin-induced intestinal secretion in the rat. Br J Pharmacol. 1981 Nov;74(3):563–569. doi: 10.1111/j.1476-5381.1981.tb10465.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Harper A. A., Macdonald A. G., Wann K. T. The effect of temperature on the nerve-blocking action of benzyl alcohol on the squid giant axon. J Physiol. 1983 May;338:51–60. doi: 10.1113/jphysiol.1983.sp014659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hubel K. A. Intestinal ion transport: effect of norepinephrine, pilocarpine, and atropine. Am J Physiol. 1976 Jul;231(1):252–257. doi: 10.1152/ajplegacy.1976.231.1.252. [DOI] [PubMed] [Google Scholar]
  15. Ilundain A., Naftalin R. J. Role of Ca(2+)-dependent regulator protein in intestinal secretion. Nature. 1979 May 31;279(5712):446–448. doi: 10.1038/279446a0. [DOI] [PubMed] [Google Scholar]
  16. Malagodi M. H., Chiou C. Y. Pharmacological evaluation of a new Ca2+ antagonist, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8): studies in smooth muscles. Eur J Pharmacol. 1974 Jun;27(1):25–33. doi: 10.1016/0014-2999(74)90198-8. [DOI] [PubMed] [Google Scholar]
  17. Munck B. G. Effects of sugar and amino acid transport on transepithelial fluxes of sodium and chloride of short circuited rat jejunum. J Physiol. 1972 Jun;223(3):699–717. doi: 10.1113/jphysiol.1972.sp009870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Munck B. G. Interactions between lysine, Na+ and Cl- transport in rat jejunum. Biochim Biophys Acta. 1970 Jun 2;203(3):424–433. doi: 10.1016/0005-2736(70)90182-3. [DOI] [PubMed] [Google Scholar]
  19. Munck B. G., Schultz S. G. Properties of the passive conductance pathway across in vitro rat jejunum. J Membr Biol. 1974;16(2):163–174. doi: 10.1007/BF01872412. [DOI] [PubMed] [Google Scholar]
  20. Seeman P. The membrane actions of anesthetics and tranquilizers. Pharmacol Rev. 1972 Dec;24(4):583–655. [PubMed] [Google Scholar]
  21. Smith P. L., Field M. In vitro antisecretory effects of trifluoperazine and other neuroleptics in rabbit and human small intestine. Gastroenterology. 1980 Jun;78(6):1545–1553. [PubMed] [Google Scholar]
  22. Smith R. J., Iden S. S. Phorbol myristate acetate-induced release of granule enzymes from human neutrophils: inhibition by the calcium antagonist, 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride. Biochem Biophys Res Commun. 1979 Nov 14;91(1):263–271. doi: 10.1016/0006-291x(79)90612-0. [DOI] [PubMed] [Google Scholar]
  23. Tai Y. H., Decker R. A. Mechanisms of electrolyte transport in rat ileum. Am J Physiol. 1980 Mar;238(3):G208–G212. doi: 10.1152/ajpgi.1980.238.3.G208. [DOI] [PubMed] [Google Scholar]
  24. Taylor A., Windhager E. E. Possible role of cytosolic calcium and Na-Ca exchange in regulation of transepithelial sodium transport. Am J Physiol. 1979 Jun;236(6):F505–F512. doi: 10.1152/ajprenal.1979.236.6.F505. [DOI] [PubMed] [Google Scholar]
  25. Trotter J. A., Quintana R. L. Inhibition of macrophage spreading by antagonists of cellular calcium. FEBS Lett. 1981 Jun 29;129(1):29–32. doi: 10.1016/0014-5793(81)80747-8. [DOI] [PubMed] [Google Scholar]
  26. Weiss B., Prozialeck W., Cimino M., Barnette M. S., Wallace T. L. Pharmacological regulation of calmodulin. Ann N Y Acad Sci. 1980;356:319–345. doi: 10.1111/j.1749-6632.1980.tb29621.x. [DOI] [PubMed] [Google Scholar]
  27. Zimmerman T. W., Dobbins J. W., Binder H. J. Role of calcium in the regulation of colonic secretion in the rat. Am J Physiol. 1983 May;244(5):G552–G560. doi: 10.1152/ajpgi.1983.244.5.G552. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES