Potent enhancement of [3H]nitrendipine binding in rat cerebral cortical and cardiac homogenates: A putative mechanism for the action of MDL 12,330A

H. R. Lee, J. A. Jaros, W. R. Roeske

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

[3H]Nitrendipine ([3H]NTD), a specific high-affinity calcium channel antagonist, was used to label dihydropyridine binding sites associated with calcium channels in rat cerebral cortical and cardiac homogenates. A novel lactamimide compound, MDL 12,33A, has been shown previously to have negative inotropic and chronotropic effects in isolated working guinea-pig hearts and these effects are reversed by the administration of calcium. MDL 12,330A is potent in enhancing [3H]NTD binding in membranes prepared from the cerebral cortex and the heart, with EC50 values of 6.1 x 10-8 and 3.4 x 10-8M, respectively, at 37°C. This allosteric effect by MDL 12,330A is similar to that produced by a known calcium channel antagonist, d-cis diltiazem, which has been shown previously to enhance [3H]NTD binding at 37°C. The extent of enhancement by MDL 12,330A depends on incubation temperature (37°C>25°C>0°C). The mechanism of this enhancement by MDL 12,330A is due to a decrease in the dissociation rate constant of the dihydropyridine-calcium channel supramolecular complex. MDL 12,330A is the most potent drug thus far examined which demonstrates the enhancement of [3H]NTD binding.

Original languageEnglish (US)
Pages (from-to)611-616
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume233
Issue number3
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Potent enhancement of [<sup>3</sup>H]nitrendipine binding in rat cerebral cortical and cardiac homogenates: A putative mechanism for the action of MDL 12,330A'. Together they form a unique fingerprint.

  • Cite this