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. 1982 Dec;77(4):661–666. doi: 10.1111/j.1476-5381.1982.tb09344.x

Effects of calmodulin antagonists on tension and cellular calcium content in depolarized vascular and intestinal smooth muscles.

H Karaki, K Murakami, H Nakagawa, H Ozaki, N Urakawa
PMCID: PMC2044672  PMID: 7150873

Abstract

1 Several putative calmodulin antagonists have been examined for their inhibitory action on muscle tension and cellular Ca content in the K-depolarized vascular and intestinal smooth muscles. 2 The 65.4 mM K-induced sustained contraction in the media-intimal layer of rabbit aorta and the 45.4 mM K-induced sustained contraction in guinea-pig taenia coli were inhibited by the calmodulin antagonists, prenylamine, chlorpromazine, N2-dansyl-L-arginine-4-t-butylpiperadine amide (No. 233), and N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), and also by the organic Ca antagonists, verapamil and diltiazem. 3 The cellular Ca content in rabbit aorta and guinea-pig taenia coli as measured by a modified lanthanum technique increased in the high-K solutions. The increments were inhibited by these antagonists at concentrations similar to those required to inhibit the K-induced contractions. However, W-7 did not change (in aorta) or only slightly decreased (in taenia coli) the K-induced increase in the cellular Ca content. 4 A high concentration (2 X 10(-4)M) of W-7 increased the resting cellular Ca content without increasing the muscle tension in aorta. The increment was inhibited by verapamil, sodium nitroprusside or hypoxia (N2 aeration). 5 It is suggested that the inhibitory effects of prenylamine, chlorpromazine and No. 233 may be attributed mainly to the Ca antagonistic effect whereas W-7 may inhibit the process beyond the transmembrane Ca influx.

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Selected References

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

  1. Asano M., Suzuki Y., Hidaka H. Effects of various calmodulin antagonists on contraction of rabbit aortic strips. J Pharmacol Exp Ther. 1982 Jan;220(1):191–196. [PubMed] [Google Scholar]
  2. Caroni P., Carafoli E. The Ca2+-pumping ATPase of heart sarcolemma. Characterization, calmodulin dependence, and partial purification. J Biol Chem. 1981 Apr 10;256(7):3263–3270. [PubMed] [Google Scholar]
  3. Chaturvedi A. K., Landon E. J., Rama Sastry B. V. Influence of chlorpromazine on calcium movements and contractile responses of guinea-pig ileum longitudinal smooth muscle to agonists. Arch Int Pharmacodyn Ther. 1978 Nov;236(1):109–124. [PubMed] [Google Scholar]
  4. Dabrowska R., Sherry J. M., Aromatorio D. K., Hartshorne D. J. Modulator protein as a component of the myosin light chain kinase from chicken gizzard. Biochemistry. 1978 Jan 24;17(2):253–258. doi: 10.1021/bi00595a010. [DOI] [PubMed] [Google Scholar]
  5. FURCHGOTT R. F. Spiral-cut strip of rabbit aorta for in vitro studies of responses of arterial smooth muscle. Methods Med Res. 1960;8:177–186. [PubMed] [Google Scholar]
  6. Fleckenstein A., Grün G., Tritthart H., Byon K. Uterus-Relaxation durch hochaktive Ca plus,plus-antagonistische Hemmstoffe der elektro-mechanischen Koppelung wie Isoptin (Verapamil, Iproveratril), Substanz D 600 und Segontin (Prenylamin). Versuche am isolierten Uterus virgineller Ratten. Klin Wochenschr. 1971 Jan;49(1):32–41. doi: 10.1007/BF01494064. [DOI] [PubMed] [Google Scholar]
  7. Gopinath R. M., Vincenzi F. F. Phosphodiesterase protein activator mimics red blood cell cytoplasmic activator of (Ca2+-Mg2+)ATPase. Biochem Biophys Res Commun. 1977 Aug 22;77(4):1203–1209. doi: 10.1016/s0006-291x(77)80107-1. [DOI] [PubMed] [Google Scholar]
  8. Hartshorne D. J., Mrwa U. Regulation of smooth muscle actomyosin. Blood Vessels. 1982;19(1):1–18. doi: 10.1159/000158369. [DOI] [PubMed] [Google Scholar]
  9. Hidaka H., Asano M., Iwadare S., Matsumoto I., Totsuka T., Aoki N. A novel vascular relaxing agent, N-(6--aminohexyl)-5-chloro-1-naphthalensulfonamide which affects vascular smooth muscle actomyosin. J Pharmacol Exp Ther. 1978 Oct;207(1):8–15. [PubMed] [Google Scholar]
  10. 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]
  11. Hogaboom G. K., Fedan J. S. Calmodulin stimulation of calcium uptake and (Ca2+-Mg2+)-ATPase activities in microsomes from canine tracheal smooth muscle. Biochem Biophys Res Commun. 1981 Mar 31;99(2):737–744. doi: 10.1016/0006-291x(81)91805-2. [DOI] [PubMed] [Google Scholar]
  12. Ito K., Karaki H., Urakawa N. The mode of contractile action of palytoxin on vascular smooth muscle. Eur J Pharmacol. 1977 Nov 1;46(1):9–14. doi: 10.1016/0014-2999(77)90137-6. [DOI] [PubMed] [Google Scholar]
  13. Jarrett H. W., Penniston J. T. Partial purification of the Ca2+-Mg2+ ATPase activator from human erythrocytes: its similarity to the activator of 3':5' - cyclic nucleotide phosphodiesterase. Biochem Biophys Res Commun. 1977 Aug 22;77(4):1210–1216. doi: 10.1016/s0006-291x(77)80108-3. [DOI] [PubMed] [Google Scholar]
  14. Kanamori M., Naka M., Asano M., Hidaka H. Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and other calmodulin antagonists (calmodulin interacting agents) on calcium-induced contraction of rabbit aortic strips. J Pharmacol Exp Ther. 1981 May;217(2):494–499. [PubMed] [Google Scholar]
  15. Karaki H., Hester R. K., Weiss G. B. Cellular basis of nitroprusside-induced relaxation of graded responses to norepinephrine and potassium in canine renal arteries. Arch Int Pharmacodyn Ther. 1980 Jun;245(2):198–210. [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Karaki H., Weiss G. B. Effects of stimulatory agents on mobilization of high and low affinity site 45Ca in rabbit aortic smooth muscle. J Pharmacol Exp Ther. 1980 Jun;213(3):450–455. [PubMed] [Google Scholar]
  19. Karaki H., Weiss G. B. Inhibitors of mitochondrial Ca++ uptake dissociate potassium-induced tension responses from increased 45Ca retention in rabbit aortic smooth muscle. Blood Vessels. 1981;18(1-2):28–35. doi: 10.1159/000158335. [DOI] [PubMed] [Google Scholar]
  20. Levin R. M., Weiss B. Mechanism by which psychotropic drugs inhibit adenosine cyclic 3',5'-monophosphate phosphodiesterase of brain. Mol Pharmacol. 1976 Jul;12(4):581–589. [PubMed] [Google Scholar]
  21. Mikawa T., Nonomura Y., Hirata M., Ebashi S., Kakiuchi S. Involvement of an acidic protein in regulation of smooth muscle contraction by the tropomyosin-leiotonin system. J Biochem. 1978 Dec;84(6):1633–1636. doi: 10.1093/oxfordjournals.jbchem.a132290. [DOI] [PubMed] [Google Scholar]
  22. Shibata S., Carrier O., Jr Antagonizing action of chlorpromazine, dibenamine, and phenoxybenzamine on potassium-induced contraction. Can J Physiol Pharmacol. 1967 Jul;45(4):587–596. doi: 10.1139/y67-071. [DOI] [PubMed] [Google Scholar]
  23. Van Breemen C., McNaughton E. The separation of cell membrane calcium transport from extracellular calcium exchange in vascular smooth muscle. Biochem Biophys Res Commun. 1970 May 22;39(4):567–574. doi: 10.1016/0006-291x(70)90241-x. [DOI] [PubMed] [Google Scholar]
  24. Yagi K., Yazawa M., Kakiuchi S., Ohshima M., Uenishi K. Identification of an activator protein for myosin light chain kinase as the Ca2+-dependent modulator protein. J Biol Chem. 1978 Mar 10;253(5):1338–1340. [PubMed] [Google Scholar]

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