Abstract
Antagonism between either the dihydropyridine calcium agonist, Bay k 8644, or high external Ca2+ and the calcium antagonists, nifedipine, verapamil and diltiazem, and Mn2+ was investigated in canine isolated ventricular trabeculae. Bay k 8644 (10(-7)-10(-5)M) produced a slowly developing increase in developed tension which reached a maximum at 10(-6)M. A small decrease in the positive inotropic effect of Bay k 8644 at 10(-5)M was probably due to the negative inotropic effect of the solvent, 0.5% ethanol. Bay k 8644 (10(-7)-10(-5)M) produced a rightward parallel shift of the concentration-response curves for the negative inotropic effects of nifedipine (10(-8)-10(-5)M) and verapamil (10(-7)-3 X 10(-5)M). The slopes of the Schild plots were -0.92 for nifedipine (pA2 value = 6.58) and -0.48 for verapamil. Bay k 8644 (10(-6) and 10(-5)M) produced only a slight rightward shift of the concentration-response curves for the negative inotropic effect of diltiazem (10(-7)-3 X 10(-5)M) and did not affect the negative inotropic effect of Mn2+ (10(-4)-10(-2)M). Addition of 2.5 X 10(-3)M Ca2+ (5.05 X 10(-3)M Ca2+) to the medium produced a greater maximum positive inotropic effect than Bay k 8644. The concentration-response curves for the negative inotropic effects of nifedipine, verapamil and diltiazem obtained under these conditions were not essentially different from those under control conditions (2.55 X 10(-3)M Ca2+).(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bellemann P. Binding properties of a novel calcium channel activating dihydropyridine in monolayer cultures of beating myocytes. FEBS Lett. 1984 Feb 13;167(1):88–92. doi: 10.1016/0014-5793(84)80838-8. [DOI] [PubMed] [Google Scholar]
- Ehlert F. J., Itoga E., Roeske W. R., Yamamura H. I. The interaction of [3H]nitrendipine with receptors for calcium antagonists in the cerebral cortex and heart of rats. Biochem Biophys Res Commun. 1982 Feb 11;104(3):937–943. doi: 10.1016/0006-291x(82)91339-0. [DOI] [PubMed] [Google Scholar]
- Endoh M., Yanagisawa T., Taira N. Dissociation of cyclic AMP and contractile responses to isoprenaline: effects of a dihydropyridine derivative, nicardipine (YC-93), on canine ventricular muscle. Eur J Pharmacol. 1980 Oct 17;67(2-3):225–233. doi: 10.1016/0014-2999(80)90502-6. [DOI] [PubMed] [Google Scholar]
- Ferry D. R., Glossmann H. Evidence of multiple receptor sites within the putative calcium channel. Naunyn Schmiedebergs Arch Pharmacol. 1982 Oct;321(1):80–83. doi: 10.1007/BF00586355. [DOI] [PubMed] [Google Scholar]
- García A. G., Sala F., Reig J. A., Viniegra S., Frías J., Fontériz R., Gandía L. Dihydropyridine BAY-K-8644 activates chromaffin cell calcium channels. Nature. 1984 May 3;309(5963):69–71. doi: 10.1038/309069a0. [DOI] [PubMed] [Google Scholar]
- Hagiwara S., Byerly L. Calcium channel. Annu Rev Neurosci. 1981;4:69–125. doi: 10.1146/annurev.ne.04.030181.000441. [DOI] [PubMed] [Google Scholar]
- Murphy K. M., Gould R. J., Largent B. L., Snyder S. H. A unitary mechanism of calcium antagonist drug action. Proc Natl Acad Sci U S A. 1983 Feb;80(3):860–864. doi: 10.1073/pnas.80.3.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Satoh K., Wada Y., Taira N. Differential effects of Bay k 8644, a presumed calcium channel activator, on sinoatrial nodal and ventricular automaticity of the dog heart. Naunyn Schmiedebergs Arch Pharmacol. 1984 Jun;326(2):190–192. doi: 10.1007/BF00517319. [DOI] [PubMed] [Google Scholar]
- Schramm M., Thomas G., Towart R., Franckowiak G. Activation of calcium channels by novel 1,4-dihydropyridines. A new mechanism for positive inotropics or smooth muscle stimulants. Arzneimittelforschung. 1983;33(9):1268–1272. [PubMed] [Google Scholar]
- 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]