Abstract
[3H]Nitrendipine binds with high affinity to brain membranes with a drug specificity indicating association with sites mediating the pharmacologic actions of dihydropyridine slow-calcium-channel antagonist drugs. In brain membranes, [3H]nitrendipine binding is absolutely dependent on the presence of calcium ions. Interactions of cation with [3H]nitrendipine binding sites correlate with their physiologic actions at voltage-dependent calcium channels. Ions such as strontium and barium, which mimic calcium physiologically, share the action of calcium in enhancing [3H]nitrendipine binding. Ions such as lanthanum an cobalt, which block the effects of calcium, can inhibit [3H]nitrendipine binding and block the stimulating actions of calcium. The ability to monitor the influence of ions on an agonist-antagonist continuum at [3H]nitrendipine binding sites provides a molecular probe to explore the regulation of cellular function by calcium and other cations.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Antman E. M., Stone P. H., Muller J. E., Braunwald E. Calcium channel blocking agents in the treatment of cardiovascular disorders. Part I: Basic and clinical electrophysiologic effects. Ann Intern Med. 1980 Dec;93(6):875–885. doi: 10.7326/0003-4819-93-6-875. [DOI] [PubMed] [Google Scholar]
- Bellemann P., Ferry D., Lübbecke F., Glossman H. [3H]-Nitrendipine, a potent calcium antagonist, binds with high affinity to cardiac membranes. Arzneimittelforschung. 1981;31(12):2064–2067. [PubMed] [Google Scholar]
- Bolger G. T., Gengo P. J., Luchowski E. M., Siegel H., Triggle D. J., Janis R. A. High affinity binding of a calcium channel antagonist to smooth and cardiac muscle. Biochem Biophys Res Commun. 1982 Feb 26;104(4):1604–1609. doi: 10.1016/0006-291x(82)91436-x. [DOI] [PubMed] [Google Scholar]
- Chang K. J., Jacobs S., Cuatrecasas P. Quantitative aspects of hormone-receptor interactions of high affinity. Effect of receptor concentration and measurement of dissociation constants of labeled and unlabeled hormones. Biochim Biophys Acta. 1975 Oct 6;406(2):294–303. doi: 10.1016/0005-2736(75)90011-5. [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]
- Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–166. doi: 10.1146/annurev.pa.17.040177.001053. [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]
- Hagiwara S., Byerly L. Membrane biophysics of calcium currents. Fed Proc. 1981 Jun;40(8):2220–2225. [PubMed] [Google Scholar]
- Henry P. D. Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol. 1980 Dec 1;46(6):1047–1058. doi: 10.1016/0002-9149(80)90366-5. [DOI] [PubMed] [Google Scholar]
- Murphy K. M., Snyder S. H. Calcium antagonist receptor binding sites labeled with [3H]nitrendipine. Eur J Pharmacol. 1982 Jan 22;77(2-3):201–202. doi: 10.1016/0014-2999(82)90021-8. [DOI] [PubMed] [Google Scholar]
- Reuter H. Divalent cations as charge carriers in excitable membranes. Prog Biophys Mol Biol. 1973;26:1–43. doi: 10.1016/0079-6107(73)90016-3. [DOI] [PubMed] [Google Scholar]
- Stone P. H., Antman E. M., Muller J. E., Braunwald E. Calcium channel blocking agents in the treatment of cardiovascular disorders. Part II: Hemodynamic effects and clinical applications. Ann Intern Med. 1980 Dec;93(6):886–904. doi: 10.7326/0003-4819-93-6-886. [DOI] [PubMed] [Google Scholar]