Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Mar;114(6):1289–1295. doi: 10.1111/j.1476-5381.1995.tb13345.x

Effects of semotiadil fumarate, a novel Ca2+ antagonist, on cytosolic Ca2+ level and force of contraction in porcine coronary arteries.

M Kageyama 1, T Yanagisawa 1, N Taira 1
PMCID: PMC1510365  PMID: 7620720

Abstract

1. The mechanisms of action of semotiadil fumarate, a novel Ca2+ antagonist, were examined by measuring the cytosolic Ca2+ level ([Ca2+]i) and force of contraction in porcine coronary arteries, and by determining [3H]-pyrilamine binding to bovine cerebellar membranes. 2. Semotiadil or verapamil (0.1 and 1 microM) inhibited both the high KCl-induced increases in [Ca2+]i and force in a concentration-dependent manner. 3. Histamine (30 microM) produced transient increases followed by sustained increases in [Ca2+]i and force, which were inhibited by semotiadil and verapamil (1 and 10 microM). The agents were different in that semotiadil reduced the maximum [Ca2+]i and force responses to histamine, but not pD2 values, whereas verapamil did reduce the pD2 values for histamine, but not the maximum responses. 4. Verapamil (10 microM), but not semotiadil, inhibited histamine-induced increases in [Ca2+]i and force in Ca(2+)-free solution. Neither semotiadil nor verapamil affected the increases in [Ca2+]i and force induced by caffeine. Semotiadil even at the higher concentration (10 microM) did not displace specific binding of [3H]-pyrilamine to bovine cerebellar membranes. 5. These results suggest that semotiadil inhibits both KCl- and histamine-induced contractions mainly by blocking voltage-dependent L-type Ca2+ channels.

Full text

PDF
1289

Selected References

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

  1. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  2. Chang R. S., Tran V. T., Snyder S. H. Heterogeneity of histamine H1-receptors: species variations in [3H]mepyramine binding of brain membranes. J Neurochem. 1979 Jun;32(6):1653–1663. doi: 10.1111/j.1471-4159.1979.tb02276.x. [DOI] [PubMed] [Google Scholar]
  3. Donaldson J., Hill S. J. Histamine-induced inositol phospholipid breakdown in the longitudinal smooth muscle of guinea-pig ileum. Br J Pharmacol. 1985 Jun;85(2):499–512. doi: 10.1111/j.1476-5381.1985.tb08887.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  5. Himpens B., Somlyo A. P. Free-calcium and force transients during depolarization and pharmacomechanical coupling in guinea-pig smooth muscle. J Physiol. 1988 Jan;395:507–530. doi: 10.1113/jphysiol.1988.sp016932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hirano K., Kanaide H., Abe S., Nakamura M. Effects of diltiazem on calcium concentrations in the cytosol and on force of contractions in porcine coronary arterial strips. Br J Pharmacol. 1990 Oct;101(2):273–280. doi: 10.1111/j.1476-5381.1990.tb12700.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ishikawa T., Hume J. R., Keef K. D. Modulation of K+ and Ca2+ channels by histamine H1-receptor stimulation in rabbit coronary artery cells. J Physiol. 1993 Aug;468:379–400. doi: 10.1113/jphysiol.1993.sp019777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kageyama M., Mori T., Yanagisawa T., Taira N. Is staurosporine a specific inhibitor of protein kinase C in intact porcine coronary arteries? J Pharmacol Exp Ther. 1991 Dec;259(3):1019–1026. [PubMed] [Google Scholar]
  9. Kageyama M., Nishimura K., Takada T., Miyawaki N., Yamauchi H. SD-3211, a novel benzothiazine calcium antagonist, alone and in combination with a beta-adrenoceptor antagonist, produces antihypertensive effects without affecting heart rate and atrioventricular conduction in conscious renal hypertensive dogs. J Cardiovasc Pharmacol. 1991 Jan;17(1):102–107. doi: 10.1097/00005344-199101000-00015. [DOI] [PubMed] [Google Scholar]
  10. Kalsner S., Richards R. Coronary arteries of cardiac patients are hyperreactive and contain stores of amines: a mechanism for coronary spasm. Science. 1984 Mar 30;223(4643):1435–1437. doi: 10.1126/science.6701530. [DOI] [PubMed] [Google Scholar]
  11. Matsumoto T., Kanaide H., Nishimura J., Kuga T., Kobayashi S., Nakamura M. Histamine-induced calcium transients in vascular smooth muscle cells: effects of verapamil and diltiazem. Am J Physiol. 1989 Aug;257(2 Pt 2):H563–H570. doi: 10.1152/ajpheart.1989.257.2.H563. [DOI] [PubMed] [Google Scholar]
  12. Miyawaki N., Furuta T., Shigei T., Yamauchi H., Iso T. Cardiovascular characterization of SD-3211, a novel benzothiazine calcium channel blocker, in isolated rabbit hearts. Life Sci. 1991;48(20):1903–1909. doi: 10.1016/0024-3205(91)90222-w. [DOI] [PubMed] [Google Scholar]
  13. Miyawaki N., Furuta T., Shigei T., Yamauchi H., Iso T. Electrophysiological properties of SD-3211, a novel putative Ca2+ antagonist, in isolated guinea pig and rabbit hearts. J Cardiovasc Pharmacol. 1990 Nov;16(5):769–775. doi: 10.1097/00005344-199011000-00012. [DOI] [PubMed] [Google Scholar]
  14. Mori T., Yanagisawa T., Taira N. Histamine increases vascular tone and intracellular calcium level using both intracellular and extracellular calcium in porcine coronary arteries. Jpn J Pharmacol. 1990 Feb;52(2):263–271. doi: 10.1254/jjp.52.263. [DOI] [PubMed] [Google Scholar]
  15. Mori T., Yanagisawa T., Taira N. Phorbol 12,13-dibutyrate increases vascular tone but has a dual action on intracellular calcium levels in porcine coronary arteries. Naunyn Schmiedebergs Arch Pharmacol. 1990 Mar;341(3):251–255. doi: 10.1007/BF00169739. [DOI] [PubMed] [Google Scholar]
  16. Nakayama K., Morimoto K., Nozawa Y., Tanaka Y. Calcium antagonistic and binding properties of semotiadil (SD-3211), a benzothiazine derivative assessed in cerebral and coronary arteries. J Cardiovasc Pharmacol. 1992 Sep;20(3):380–391. doi: 10.1097/00005344-199209000-00007. [DOI] [PubMed] [Google Scholar]
  17. Nishimura K., Miyawaki N., Yamauchi H., Iso T. Tissue selectivity of the novel calcium antagonist sesamodil fumarate in isolated smooth muscles and cardiac muscles. Arzneimittelforschung. 1990 Mar;40(3):244–248. [PubMed] [Google Scholar]
  18. Okada Y., Yanagisawa T., Taira N. BRL 38227 (levcromakalim)-induced hyperpolarization reduces the sensitivity to Ca2+ of contractile elements in canine coronary artery. Naunyn Schmiedebergs Arch Pharmacol. 1993 Apr;347(4):438–444. doi: 10.1007/BF00165396. [DOI] [PubMed] [Google Scholar]
  19. Rembold C. M., Murphy R. A. Myoplasmic [Ca2+] determines myosin phosphorylation in agonist-stimulated swine arterial smooth muscle. Circ Res. 1988 Sep;63(3):593–603. doi: 10.1161/01.res.63.3.593. [DOI] [PubMed] [Google Scholar]
  20. Sato K., Ozaki H., Karaki H. Changes in cytosolic calcium level in vascular smooth muscle strip measured simultaneously with contraction using fluorescent calcium indicator fura 2. J Pharmacol Exp Ther. 1988 Jul;246(1):294–300. [PubMed] [Google Scholar]
  21. Shimokawa H., Tomoike H., Nabeyama S., Yamamoto H., Araki H., Nakamura M., Ishii Y., Tanaka K. Coronary artery spasm induced in atherosclerotic miniature swine. Science. 1983 Aug 5;221(4610):560–562. doi: 10.1126/science.6408736. [DOI] [PubMed] [Google Scholar]
  22. Takada T., Miyawaki N., Kageyama M., Matsuno K., Ishida N., Yamauchi H., Iso T. Antihypertensive effect of a novel calcium antagonist, SD-3211, in experimental hypertensive rats. J Cardiovasc Pharmacol. 1991 Dec;18(6):855–862. doi: 10.1097/00005344-199112000-00011. [DOI] [PubMed] [Google Scholar]
  23. Teramoto N. Mechanisms of the inhibitory action of semotiadil fumarate, a novel Ca antagonist, on the voltage-dependent Ca current in smooth muscle cells of the rabbit portal vein. Jpn J Pharmacol. 1993 Mar;61(3):183–195. doi: 10.1254/jjp.61.183. [DOI] [PubMed] [Google Scholar]
  24. Yanagisawa T., Kawada M., Taira N. Nitroglycerin relaxes canine coronary arterial smooth muscle without reducing intracellular Ca2+ concentrations measured with fura-2. Br J Pharmacol. 1989 Oct;98(2):469–482. doi: 10.1111/j.1476-5381.1989.tb12620.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yanagisawa T., Okada Y. KCl depolarization increases Ca2+ sensitivity of contractile elements in coronary arterial smooth muscle. Am J Physiol. 1994 Aug;267(2 Pt 2):H614–H621. doi: 10.1152/ajpheart.1994.267.2.H614. [DOI] [PubMed] [Google Scholar]
  26. Yoneyama F., Yamada H., Satoh K., Taira N. Cardiac versus coronary dilator effects of SD-3211, a new nondihydropyridine calcium antagonist, in isolated, blood-perfused dog hearts. Cardiovasc Drugs Ther. 1990 Dec;4(6):1469–1476. doi: 10.1007/BF02026494. [DOI] [PubMed] [Google Scholar]

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

RESOURCES