Abstract
Depolarization of NG108-15 (neuroblastoma-glioma) cells causes an increase in 45Ca2+ influx. This effect is blocked by low concentrations of dihydropyridines such as nitrendipine and by other blockers of voltage-sensitive calcium channels such as D-600, diltiazem, and Cd2+. Two other dihydropyridines, BAY K8644 and CGP 28392, have the opposite effect. Low concentrations of these compounds enhance depolarization-induced 45Ca2+ influxes. BAY K8644 is more effective than CGP 28392. Both agents have no effect on fluxes measured under nondepolarizing conditions. The effects of BAY K8644 and CGP 28392 can be inhibited by nitrendipine, D-600, diltiazem, or Cd2+. Whereas the interaction between nitrendipine and BAY K8644 is shown to be competitive in nature, that between BAY K8644 and D-600 is shown to be noncompetitive. These results indicate that dihydropyridines show a variety of effects on calcium channels, ranging from agonistic through partially agonistic to antagonistic. Moreover, the results also indicate that dihydropyridines and D-600 exert their effects on calcium channels at different sites.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Avruch J., Wallach D. F. Preparation and properties of plasma membrane and endoplasmic reticulum fragments from isolated rat fat cells. Biochim Biophys Acta. 1971 Apr 13;233(2):334–347. doi: 10.1016/0005-2736(71)90331-2. [DOI] [PubMed] [Google Scholar]
- Bolger G. T., Gengo P., Klockowski R., Luchowski E., Siegel H., Janis R. A., Triggle A. M., Triggle D. J. Characterization of binding of the Ca++ channel antagonist, [3H]nitrendipine, to guinea-pig ileal smooth muscle. J Pharmacol Exp Ther. 1983 May;225(2):291–309. [PubMed] [Google Scholar]
- DePover A., Matlib M. A., Lee S. W., Dubé G. P., Grupp I. L., Grupp G., Schwartz A. Specific binding of [3H]nitrendipine to membranes from coronary arteries and heart in relation to pharmacological effects. Paradoxical stimulation by diltiazem. Biochem Biophys Res Commun. 1982 Sep 16;108(1):110–117. doi: 10.1016/0006-291x(82)91838-1. [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]
- Freedman S. B., Dawson G., Villereal M. L., Miller R. J. Identification and characterization of voltage-sensitive calcium channels in neuronal clonal cell lines. J Neurosci. 1984 Jun;4(6):1453–1467. doi: 10.1523/JNEUROSCI.04-06-01453.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Himori N., Ono H., Taira N. Simultaneous assessment of effects of coronary vasodilators on the coronary blood flow and the myocardial contractility by using the blood-perfused canine papillary muscle. Jpn J Pharmacol. 1976 Aug;26(4):427–435. doi: 10.1254/jjp.26.427. [DOI] [PubMed] [Google Scholar]
- Janis R. A., Triggle D. J. New developments in Ca2+ channel antagonists. J Med Chem. 1983 Jun;26(6):775–785. doi: 10.1021/jm00360a001. [DOI] [PubMed] [Google Scholar]
- Miller R. J., Freedman S. B. Are dihydropyridine binding sites voltage sensitive calcium channels? Life Sci. 1984 Mar 26;34(13):1205–1221. doi: 10.1016/0024-3205(84)90543-5. [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]
- 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]
- Yamamura H. I., Schoemaker H., Boles R. G., Roeske W. R. Diltiazem enhancement of [3H]nitrendipine binding to calcium channel associated drug receptor sites in rat brain synaptosomes. Biochem Biophys Res Commun. 1982 Sep 30;108(2):640–646. doi: 10.1016/0006-291x(82)90877-4. [DOI] [PubMed] [Google Scholar]