Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1983 Sep;72(3):955–964. doi: 10.1172/JCI111067

Role of calcium and calmodulin in activation of the oxyntic cell by histamine and carbamylcholine in the guinea pig.

W Walker, A Vinik, A Heldsinger, R Kaveh
PMCID: PMC1129261  PMID: 6309912

Abstract

The role of calcium in stimulation of the oxyntic cell by histamine and carbamylcholine was studied using a sensitive quantitative cytochemical staining technique that measures oxyntic cell hydroxyl ion production (HIP) as an index of acid secretion. Histamine (10(-17)-10(-14) M), carbamylcholine (10(-12)-10(-9) M), and extracellular calcium (10(-7)-10(-3) M) caused a linear, dose-dependent stimulation of the oxyntic cell. EGTA (10(-6) M) inhibited carbamylcholine by 50% but not histamine-stimulated activity. Lanthanum chloride (10(-6) M) caused 100% inhibition of carbamylcholine-induced activity but did not affect histamine-stimulated activity. A maximally effective dose of calcium (10(-4) M) caused additive effects on HIP at low doses of carbamylcholine without alteration of the maximal effect of carbamylcholine. Calcium (10(-4) M) did not enhance the effects of histamine. The calmodulin antagonists, trifluoperazine (10(-5) M), pimozide (10(-5) M), and a naphthalenesulfonamide (W-7), inhibited the integrated response to histamine by 54, 56, and 53%, and that of carbamylcholine by 65, 64, and 99%, respectively. Thus, extracellular calcium per se, stimulates the oxyntic cell. The action of carbamylcholine is completely dependent upon calcium/calmodulin mediation, supporting the concept that cholinergic actions are mediated via calcium-calmodulin events. Although histamine does not require extracellular or membrane calcium events to stimulate the oxyntic cell, calmodulin appears to participate in histamine action.

Full text

PDF
955

Selected References

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

  1. Bitensky L., Alaghband-Zadeh J., Chayen J. Studies on thyroid stimulating hormone and the long-acting thyroid stimulating hormone. Clin Endocrinol (Oxf) 1974 Jul;3(3):363–374. doi: 10.1111/j.1365-2265.1974.tb01811.x. [DOI] [PubMed] [Google Scholar]
  2. Chambers D. J., Dunham J., Zanelli J. M., Parsons J. A., Bitensky L., Chayen J. A sensitive bioassay of parathyroid hormone in plasma. Clin Endocrinol (Oxf) 1978 Oct;9(4):375–379. doi: 10.1111/j.1365-2265.1978.tb02223.x. [DOI] [PubMed] [Google Scholar]
  3. Cheung W. Y. Calmodulin plays a pivotal role in cellular regulation. Science. 1980 Jan 4;207(4426):19–27. doi: 10.1126/science.6243188. [DOI] [PubMed] [Google Scholar]
  4. Conn P. M., Rogers D. C., Sandhu F. S. Alteration of the intracellular calcium level stimulates gonadotropin release from cultured rat anterior pituitary cells. Endocrinology. 1979 Nov;105(5):1122–1127. doi: 10.1210/endo-105-5-1122. [DOI] [PubMed] [Google Scholar]
  5. Conn P. M., Rogers D. C., Sheffield T. Inhibition of gonadotropin-releasing hormone-stimulated luteinizing hormone release by pimozide: evidence for a site of action after calcium mobilization. Endocrinology. 1981 Oct;109(4):1122–1126. doi: 10.1210/endo-109-4-1122. [DOI] [PubMed] [Google Scholar]
  6. Cross S. A. Ultrastructural localisation of carbonic anhydrase in rat stomach parietal cells. Histochemie. 1970;22(3):219–225. doi: 10.1007/BF00306098. [DOI] [PubMed] [Google Scholar]
  7. Curry D. L., Bennett L. L., Grodsky G. M. Requirement for calcium ion in insulin secretion by the perfused rat pancreas. Am J Physiol. 1968 Jan;214(1):174–178. doi: 10.1152/ajplegacy.1968.214.1.174. [DOI] [PubMed] [Google Scholar]
  8. Daly J. R., Alaghband-Zadeh J., Loveridge N., Chayen J. The cytochemical bioassay of corticotropin (ACTH). Ann N Y Acad Sci. 1977 Oct 28;297:242–259. doi: 10.1111/j.1749-6632.1977.tb41857.x. [DOI] [PubMed] [Google Scholar]
  9. Daly J. R., Fleisher M. R., Chambers D. J., Bitensky L., Chayen J. Application of the cytochemical bioassay for corticotrophin to clinical and physiological studies in man. Clin Endocrinol (Oxf) 1974 Jul;3(3):335–345. doi: 10.1111/j.1365-2265.1974.tb01807.x. [DOI] [PubMed] [Google Scholar]
  10. Douglas W. W. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. Br J Pharmacol. 1968 Nov;34(3):451–474. doi: 10.1111/j.1476-5381.1968.tb08474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gardner J. D., Jackson M. J., Batzri S., Jensen R. T. Potential mechanisms of interaction among secretagogues. Gastroenterology. 1978 Feb;74(2 Pt 2):348–354. [PubMed] [Google Scholar]
  12. Hansson H. P. Histochemical demonstration of carbonic anhydrase activity. Histochemie. 1967;11(2):112–128. doi: 10.1007/BF00571716. [DOI] [PubMed] [Google Scholar]
  13. Hersey S. J., High W. L. On the mechanism of acid secretory inhibition by acetazolamide. Biochim Biophys Acta. 1971 Jun 1;233(3):604–609. doi: 10.1016/0005-2736(71)90159-3. [DOI] [PubMed] [Google Scholar]
  14. Hidaka H., Yamaki T., Naka M., Tanaka T., Hayashi H., Kobayashi R. Calcium-regulated modulator protein interacting agents inhibit smooth muscle calcium-stimulated protein kinase and ATPase. Mol Pharmacol. 1980 Jan;17(1):66–72. [PubMed] [Google Scholar]
  15. Landry Y., Amellal M., Ruckstuhl M. Can calmodulin inhibitors be used to probe calmodulin effects? Biochem Pharmacol. 1981 Jul 15;30(14):2031–2032. doi: 10.1016/0006-2952(81)90217-3. [DOI] [PubMed] [Google Scholar]
  16. Langer G. A., Frank J. S. Lanthanum in heart cell culture. Effect on calcium exchange correlated with its localization. J Cell Biol. 1972 Sep;54(3):441–455. doi: 10.1083/jcb.54.3.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Loveridge N. A quantitative cytochemical method for measuring carbonic anhydrase activity. Histochem J. 1978 May;10(3):361–372. doi: 10.1007/BF01007566. [DOI] [PubMed] [Google Scholar]
  18. Loveridge N., Bloom S. R., Welbourn R. B., Chayen J. Quantitative cytochemical estimation of the effect of pentagastrin (0.005-5 pg-ml) and of plasma gastrin on the guinea-pig fundus in vitro. Clin Endocrinol (Oxf) 1974 Jul;3(3):389–396. doi: 10.1111/j.1365-2265.1974.tb01814.x. [DOI] [PubMed] [Google Scholar]
  19. Maren T. H. Carbonic anhydrase: chemistry, physiology, and inhibition. Physiol Rev. 1967 Oct;47(4):595–781. doi: 10.1152/physrev.1967.47.4.595. [DOI] [PubMed] [Google Scholar]
  20. Means A. R., Dedman J. R. Calmodulin in endocrine cells and its multiple roles in hormone action. Mol Cell Endocrinol. 1980 Sep;19(3):215–227. doi: 10.1016/0303-7207(80)90052-0. [DOI] [PubMed] [Google Scholar]
  21. Nishikawa M., Hidaka H. Role of calmodulin in platelet aggregation. Structure-activity relationship of calmodulin antagonists. J Clin Invest. 1982 Jun;69(6):1348–1355. doi: 10.1172/JCI110574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Osborn M., Weber K. Damage of cellular functions by trifluoperazine, a calmodulin-specific drug. Exp Cell Res. 1980 Dec;130(2):484–488. doi: 10.1016/0014-4827(80)90033-6. [DOI] [PubMed] [Google Scholar]
  23. POWELL D. W., ROBBINS R. C., BOYETT J. D., HIRSCHOWITZ B. I. Evaluation of the gastric Na:H exchange mechanism using histamine and diamox. Am J Physiol. 1962 Feb;202:293–301. doi: 10.1152/ajplegacy.1962.202.2.293. [DOI] [PubMed] [Google Scholar]
  24. Rasmussen H. Calcium and cAMP in stimulus-response coupling. Ann N Y Acad Sci. 1980;356:346–353. doi: 10.1111/j.1749-6632.1980.tb29622.x. [DOI] [PubMed] [Google Scholar]
  25. Roufogalis B. D. Phenothiazine antagonism of calmodulin: a structurally-nonspecific interaction. Biochem Biophys Res Commun. 1981 Feb 12;98(3):607–613. doi: 10.1016/0006-291x(81)91157-8. [DOI] [PubMed] [Google Scholar]
  26. Rutten M. J., Machen T. E. Histamine, cyclic AmP, and activation events in piglet gastric mucosa in vitro. Gastroenterology. 1981 May;80(5 Pt 1):928–937. [PubMed] [Google Scholar]
  27. Schreurs V. V., Swarts H. G., De Pont J. J., Bonting S. L. Role of calcium in exocrine pancreatic secretion. II. Comparison of the effects of carbachol and the inophore A-23187 on enzyme secretion and calcium movements in rabbit pancreas. Biochim Biophys Acta. 1976 Jan 21;419(2):320–330. doi: 10.1016/0005-2736(76)90358-8. [DOI] [PubMed] [Google Scholar]
  28. Shapiro B., Pienta K., Heldsinger A., Vinik A. I. Somatostatin is an agonist and noncompetitive antagonist of gastrin in oxyntic cell function. Endocrinology. 1981 Oct;109(4):1117–1121. doi: 10.1210/endo-109-4-1117. [DOI] [PubMed] [Google Scholar]
  29. Stoclet J. C. An ubiquitous protein which regulates calcium-dependent cellular functions and calcium movements. Biochem Pharmacol. 1981 Jul 1;30(13):1723–1729. doi: 10.1016/0006-2952(81)90001-0. [DOI] [PubMed] [Google Scholar]
  30. Sung C. P., Jenkins B. C., Burns L. R., Hackney V., Spenney J. G., Sachs G., Wiebelhaus V. D. Adenyl and guanyl cyclase in rabbit gastric mucosa. Am J Physiol. 1973 Dec;225(6):1359–1363. doi: 10.1152/ajplegacy.1973.225.6.1359. [DOI] [PubMed] [Google Scholar]
  31. Wakasugi H., Stolze H., Haase W., Schulz I. Effect of La3+ on secretagogue-induced Ca2+ fluxes in rat isolated pancreatic acinar cells. Am J Physiol. 1981 Apr;240(4):G281–G289. doi: 10.1152/ajpgi.1981.240.4.G281. [DOI] [PubMed] [Google Scholar]
  32. Weiss B., Levin R. M. Mechanism for selectively inhibiting the activation of cyclic nucleotide phosphodiesterase and adenylate cyclase by antipsychotic agents. Adv Cyclic Nucleotide Res. 1978;9:285–303. [PubMed] [Google Scholar]
  33. Weiss G. B., Goodman F. R. Effects of lanthanum on contraction, calcium distribution and Ca45 movements in intestinal smooth muscle. J Pharmacol Exp Ther. 1969 Sep;169(1):46–55. [PubMed] [Google Scholar]
  34. Wollheim C. B., Sharp G. W. Regulation of insulin release by calcium. Physiol Rev. 1981 Oct;61(4):914–973. doi: 10.1152/physrev.1981.61.4.914. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES