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. 1986 Oct;89(2):367–375. doi: 10.1111/j.1476-5381.1986.tb10269.x

Inhibition of calcium channels by harmaline and other harmala alkaloids in vascular and intestinal smooth muscles.

H Karaki, T Kishimoto, H Ozaki, K Sakata, H Umeno, N Urakawa
PMCID: PMC1916999  PMID: 3779216

Abstract

Effects of harmaline and other harmala alkaloids on the contractions induced in the vascular smooth muscle of rabbit aorta and intestinal smooth muscle of taenia isolated from guinea-pig caecum were examined. In rabbit isolated aorta, harmaline inhibited the sustained contraction induced by 65.4 mM K+ with an IC50 (concentration needed for 50% inhibition) of 4.6 X 10(-5) M. This inhibitory effect on high K+-induced contraction was antagonized by raising the concentration of external Ca2+ but not by Bay K 8644, a Ca2+ channel facilitator. Harmaline also inhibited the sustained contraction induced by noradrenaline (10(-6) M) with an IC50 of 7.6 X 10(-5) M. The inhibitory effects on noradrenaline-induced contractions were not antagonized by raising the external Ca2+ concentrations or by Bay K 8644. In guinea-pig taenia, harmaline inhibited the 45.4 mM K+-induced contraction with an IC50 of 6.8 X 10(-5) M and the carbachol (10(-6) M)-induced contraction with an IC50 of 7.0 X 10(-5) M. The inhibitory effects on both high K+- and carbachol-induced contractions were antagonized by raising the external Ca2+ concentrations but not by Bay K 8644. Harmaline, at the concentrations needed to inhibit the muscle contraction, inhibited the increase in 45Ca2+ uptake induced by high K+, noradrenaline and carbachol in aorta and taenia. Harmaline did not change the cellular Na+ and ATP contents in resting and high K+ stimulated taenia. Other harmala alkaloids also inhibited the contractions in these smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Becker J. H., Willis J. S. The effect of harmaline on unidirectional potassium fluxes and ouabain binding in renal cell cultures. Biochim Biophys Acta. 1983 Jan 5;727(1):144–150. doi: 10.1016/0005-2736(83)90378-4. [DOI] [PubMed] [Google Scholar]
  2. Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
  3. Bose D. Mechanism of mechanical inhibition of smooth muscle by ouabain. Br J Pharmacol. 1975 Sep;55(1):111–116. doi: 10.1111/j.1476-5381.1975.tb07618.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brading A. F., Sneddon P. Evidence for multiple sources of calcium for activation of the contractile mechanism of guinea-pig taenia coli on stimulation with carbachol. Br J Pharmacol. 1980 Oct;70(2):229–240. doi: 10.1111/j.1476-5381.1980.tb07928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Canessa M., Jaimovich E., de la Fuente M. Harmaline: a competitive inhibitor of Na ion in the (Na+ + K+)-ATPase system. J Membr Biol. 1973 Oct 10;13(3):263–282. doi: 10.1007/BF01868232. [DOI] [PubMed] [Google Scholar]
  6. Cauvin C., Loutzenhiser R., Van Breemen C. Mechanisms of calcium antagonist-induced vasodilation. Annu Rev Pharmacol Toxicol. 1983;23:373–396. doi: 10.1146/annurev.pa.23.040183.002105. [DOI] [PubMed] [Google Scholar]
  7. Deth R., van Breemen C. Agonist induced release of intracellular Ca2+ in the rabbit aorta. J Membr Biol. 1977 Jan 28;30(4):363–380. doi: 10.1007/BF01869677. [DOI] [PubMed] [Google Scholar]
  8. Harafuji H., Ogawa Y. Re-examination of the apparent binding constant of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid with calcium around neutral pH. J Biochem. 1980 May;87(5):1305–1312. doi: 10.1093/oxfordjournals.jbchem.a132868. [DOI] [PubMed] [Google Scholar]
  9. Hider R. C., Smart L., Suleiman M. S. The effect of harmaline and related beta-carbolines on the acetylcholine-stimulated contractions of guinea-pig ileum. Eur J Pharmacol. 1981 Apr 9;70(4):429–436. doi: 10.1016/0014-2999(81)90353-8. [DOI] [PubMed] [Google Scholar]
  10. Hider R. C., Smart L., Suleiman M. S. The effect of harmaline and related harmala alkaloids on ouabain-stimulated contractions of the guinea-pig ileum. Eur J Pharmacol. 1981 Apr 24;71(1):87–92. doi: 10.1016/0014-2999(81)90389-7. [DOI] [PubMed] [Google Scholar]
  11. Karaki H., Kubota H., Urakawa N. Mobilization of stored calcium for phasic contraction induced by norepinephrine in rabbit aorta. Eur J Pharmacol. 1979 Jun 15;56(3):237–245. doi: 10.1016/0014-2999(79)90176-6. [DOI] [PubMed] [Google Scholar]
  12. Karaki H., Nakagawa H., Urakawa N. Comparative effects of verapamil and sodium nitroprusside on contraction and 45Ca uptake in the smooth muscle of rabbit aorta, rat aorta and guinea-pig taenia coli. Br J Pharmacol. 1984 Feb;81(2):393–400. doi: 10.1111/j.1476-5381.1984.tb10091.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Karaki H., Nakagawa H., Urakawa N. Effects of calcium antagonists on release of [3H]noradrenaline in rabbit aorta. Eur J Pharmacol. 1984 Jun 1;101(3-4):177–183. doi: 10.1016/0014-2999(84)90154-7. [DOI] [PubMed] [Google Scholar]
  14. Karaki H., Suzuki T., Ozaki H., Urakawa N., Ishida Y. Dissociation of K+-induced tension and cellular Ca2+ retention in vascular and intestinal smooth muscle in normoxia and hypoxia. Pflugers Arch. 1982 Aug;394(2):118–123. doi: 10.1007/BF00582912. [DOI] [PubMed] [Google Scholar]
  15. Karaki H., Urakawa N. Possible role of endogenous catecholamines in the contractions induced in rabbit aorta by ouabain, sodium depletion and potassium depletion. Eur J Pharmacol. 1977 May 1;43(1):65–72. doi: 10.1016/0014-2999(77)90161-3. [DOI] [PubMed] [Google Scholar]
  16. Karaki H., Weiss G. B. Alterations in high and low affinity binding of 45Ca in rabbit aortic smooth muscle by norepinephrine and potassium after exposure to lanthanum and low temperature. J Pharmacol Exp Ther. 1979 Oct;211(1):86–92. [PubMed] [Google Scholar]
  17. Karaki H., Weiss G. B. Calcium channels in smooth muscle. Gastroenterology. 1984 Oct;87(4):960–970. [PubMed] [Google Scholar]
  18. Kishimoto T., Ozaki H., Urakawa N. A quantitative relationship between cellular Na accumulation and relaxation produced by ouabain in the depolarized smooth muscle of guinea-pig taenia coli. Naunyn Schmiedebergs Arch Pharmacol. 1980 Jun;312(2):199–207. doi: 10.1007/BF00569731. [DOI] [PubMed] [Google Scholar]
  19. Oashi H., Takewaki T., Okada T. Calcium and the contractile effect of carbachol in the depolarized guinea-pig taenia caecum. Jpn J Pharmacol. 1974 Aug;24(4):601–611. doi: 10.1254/jjp.24.601. [DOI] [PubMed] [Google Scholar]
  20. Saida K., Nonomura Y. Characteristics of Ca2+- and Mg2+-induced tension development in chemically skinned smooth muscle fibers. J Gen Physiol. 1978 Jul;72(1):1–14. doi: 10.1085/jgp.72.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schramm M., Thomas G., Towart R., Franckowiak G. Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature. 1983 Jun 9;303(5917):535–537. doi: 10.1038/303535a0. [DOI] [PubMed] [Google Scholar]
  22. Schultes R. E. Hallucinogens of plant origin. Science. 1969 Jan 17;163(3864):245–254. doi: 10.1126/science.163.3864.245. [DOI] [PubMed] [Google Scholar]
  23. Sepúlveda F. V., Buclon M., Robinson J. W. L'harmaline, un inhibiteur des processus de transport intestinal associés aux mouvements des ions sodium. Gastroenterol Clin Biol. 1977;1(1):87–93. [PubMed] [Google Scholar]
  24. Spedding M., Berg C. Interactions between a "calcium channel agonist", Bay K 8644, and calcium antagonists differentiate calcium antagonist subgroups in K+-depolarized smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1984 Nov;328(1):69–75. doi: 10.1007/BF00496109. [DOI] [PubMed] [Google Scholar]
  25. Suzuki T., Karaki H., Urakawa N. Mechanism of inhibition of contraction by high K, Na deficient solution in smooth muscle of guinea-pig taenia coli. Arch Int Pharmacodyn Ther. 1980 Nov;248(1):43–49. [PubMed] [Google Scholar]
  26. Van Breemen C., Aaronson P., Loutzenhiser R. Sodium-calcium interactions in mammalian smooth muscle. Pharmacol Rev. 1978 Jun;30(2):167–208. [PubMed] [Google Scholar]

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