Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1984 Jul;82(3):587–595. doi: 10.1111/j.1476-5381.1984.tb10797.x

Role of calcium ions in kinin-induced chloride secretion.

A W Cuthbert, P V Halushka, H S Margolius, J A Spayne
PMCID: PMC1987009  PMID: 6331558

Abstract

Electrogenic ion transport across the epithelium lining the descending colon of male Sprague-Dawley rats has been measured under short-circuit conditions. Responses to kallidin (lysylbradykinin) were inhibited by 70% if calcium was removed from the solution bathing the basolateral aspect of the tissue. Under identical conditions responses to prostaglandin E1 and dibutyryl cyclic adenosine monophosphate were not changed. Forskolin, which directly activates the catalytic subunit of adenylate cyclase, was inhibited by 35% by calcium removal, whereas responses to the phosphodiesterase inhibitor isobutylmethylxanthine were inhibited by 45% by the same procedure. In the absence of calcium, strontium could substitute in promoting the chloride secretory events triggered by kallidin. Magnesium ions antagonized the effects of the kinin in the presence of calcium ions in the bathing solution. The effects of kallidin were partially antagonized by verapamil and trifluoperazine and were potentiated by isobutylmethylxanthine. These results, together with earlier evidence, suggest that kinin elicits a chloride secretory response in this epithelium by stimulating the formation of prostaglandins which then activate adenylate cyclase. Extracellular calcium ions appear to have an important role in the proximal part of this cascade for prostaglandin generation. However, biochemical correlates of these biophysical responses presented in the following paper indicate a more complex role for calcium in the genesis of the kinin response.

Full text

PDF
587

Selected References

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

  1. Bareis D. L., Manganiello V. C., Hirata F., Vaughan M., Axelrod J. Bradykinin stimulates phospholipid methylation, calcium influx, prostaglandin formation, and cAMP accumulation in human fibroblasts. Proc Natl Acad Sci U S A. 1983 May;80(9):2514–2518. doi: 10.1073/pnas.80.9.2514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Brooker G., Pedone C., Barovsky K. Selective reduction of forskolin-stimulated cyclic AMP accumulation by inhibitors of protein synthesis. Science. 1983 Jun 10;220(4602):1169–1170. doi: 10.1126/science.6190226. [DOI] [PubMed] [Google Scholar]
  4. Brostrom C. O., Brostrom M. A., Wolff D. J. Calcium-dependent adenylate cyclase from rat cerebral cortex. Reversible activation by sodium fluoride. J Biol Chem. 1977 Aug 25;252(16):5677–5685. [PubMed] [Google Scholar]
  5. Cuthbert A. W., Margolius H. S. Kinins stimulate net chloride secretion by the rat colon. Br J Pharmacol. 1982 Apr;75(4):587–598. doi: 10.1111/j.1476-5381.1982.tb09178.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cuthbert A. W., Spayne J. A. Conversion of sodium channels to a form sensitive to cyclic AMP by component(s) from red cells. Br J Pharmacol. 1983 Jul;79(3):783–797. doi: 10.1111/j.1476-5381.1983.tb10017.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cuthbert A. W., Spayne J. A. Stimulation of sodium and of chloride transport in epithelia by forskolin. Br J Pharmacol. 1982 May;76(1):33–35. doi: 10.1111/j.1476-5381.1982.tb09187.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dharmsathaphorn K., Racusen L., Dobbins J. W. Effect of somatostatin on ion transport in the rat colon. J Clin Invest. 1980 Oct;66(4):813–820. doi: 10.1172/JCI109919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Forte L. R., Bylund D. B., Zahler W. L. Forskolin does not activate sperm adenylate cyclase. Mol Pharmacol. 1983 Jul;24(1):42–47. [PubMed] [Google Scholar]
  12. 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]
  13. Grenier F. C., Rollins T. E., Smith W. L. Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture. Am J Physiol. 1981 Jul;241(1):F94–104. doi: 10.1152/ajprenal.1981.241.1.F94. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Irvine R. F. How is the level of free arachidonic acid controlled in mammalian cells? Biochem J. 1982 Apr 15;204(1):3–16. doi: 10.1042/bj2040003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kimberg D. V., Field M., Gershon E., Henderson A. Effects of prostaglandins and cholera enterotoxin on intestinal mucosal cyclic AMP accumulation. Evidence against an essential role for prostaglandins in the action of toxin. J Clin Invest. 1974 Mar;53(3):941–949. doi: 10.1172/JCI107635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee K. S., Tsien R. W. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983 Apr 28;302(5911):790–794. doi: 10.1038/302790a0. [DOI] [PubMed] [Google Scholar]
  18. Manning D. C., Snyder S. H., Kachur J. F., Miller R. J., Field M. Bradykinin receptor-mediated chloride secretion in intestinal function. Nature. 1982 Sep 16;299(5880):256–259. doi: 10.1038/299256a0. [DOI] [PubMed] [Google Scholar]
  19. Musch M. W., Kachur J. F., Miller R. J., Field M., Stoff J. S. Bradykinin-stimulated electrolyte secretion in rabbit and guinea pig intestine. Involvement of arachidonic acid metabolites. J Clin Invest. 1983 May;71(5):1073–1083. doi: 10.1172/JCI110857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nellans H. N., Frizzell R. A., Schultz S. G. Brush-border processes and transepithelial Na and Cl transport by rabbit ileum. Am J Physiol. 1974 May;226(5):1131–1141. doi: 10.1152/ajplegacy.1974.226.5.1131. [DOI] [PubMed] [Google Scholar]
  21. Schwartzman M., Liberman E., Raz A. Bradykinin and angiotensin II activation of arachidonic acid deacylation and prostaglandin E2 formation in rabbit kidney. Hormone-sensitive versus hormone-insensitive lipid pools of arachidonic acid. J Biol Chem. 1981 Mar 10;256(5):2329–2333. [PubMed] [Google Scholar]
  22. Seamon K. B., Padgett W., Daly J. W. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3363–3367. doi: 10.1073/pnas.78.6.3363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith P. L., Welsh M. J., Stoff J. S., Frizzell R. A. Chloride secretion by canine tracheal epithelium: I. Role of intracellular c AMP levels. J Membr Biol. 1982;70(3):217–226. doi: 10.1007/BF01870564. [DOI] [PubMed] [Google Scholar]
  24. Walker R., Wilson K. A. Prostaglandins and the contractile action of bradykinin on the longitudinal muscle of rat isolated ileum. Br J Pharmacol. 1979 Dec;67(4):527–533. doi: 10.1111/j.1476-5381.1979.tb08698.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weiss B., Prozialeck W. C., Wallace T. L. Interaction of drugs with calmodulin. Biochemical, pharmacological and clinical implications. Biochem Pharmacol. 1982 Jul 1;31(13):2217–2226. doi: 10.1016/0006-2952(82)90104-6. [DOI] [PubMed] [Google Scholar]
  26. Yorio T., Henry S. L., Hodges D. H., Caffrey J. L. Role of calcium and prostaglandins in the antidiuretic hormone response. Effect of ionophore A23187. Biochem Pharmacol. 1983 Mar 15;32(6):1113–1118. doi: 10.1016/0006-2952(83)90634-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES