Characteristics of the binding of (/sup 3/H)nitrendipine to rabbit ventricular membranes: modification by other Ca++ channel antagonists and by the Ca++ channel agonist Bay K 8644

Journal Article · Mon Oct 01 04:00:00 EDT 1984 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5969815

Janis, R A; Sarmiento, J G; Maurer, S C; Bolger, G T; Triggle, D J

This study was carried out to characterize (/sup 3/H)nitrendipine binding to cardiac membranes and to test the hypothesis that high affinity binding of Ca++ channel antagonists and agonists is to Ca++ channels. Binding was specific, rapid, reversible and stereoselective. The relative order of potency of nifedipine analogs for inhibition of binding was the same as that for inhibition of smooth and cardiac muscle contraction. Results with diltiazem, verapamil and lidoflazine were consistent with the hypothesis that nondihydropyridine Ca++ channel antagonists act at one or more sites allosterically linked to the 1,4-dihydropyridine site in cardiac cells. The Ca++ channel agonist Bay K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate) displaced specifically bound (/sup 3/H)nitrendipine in an apparently competitive manner with an IC50 value of 5 nM. The results suggest that organic antagonists do not act by physically blocking the Ca++ channel. The data also support the hypothesis that the high affinity binding sites for (/sup 3/H)nitrendipine in isolated cardiac membranes are associated with Ca++ channels that are inactivated or are otherwise unavailable for opening.

• Research Organization: Miles Inst. for Preclinical Pharmacology, New Haven, CT
• OSTI ID: 5969815
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 231:1; ISSN JPETA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOVASCULAR SYSTEM
CHEMICAL BONDS
DRUGS
HEART
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MUSCLES
MYOCARDIUM
ORGANS
RABBITS
REACTION KINETICS
STEREOCHEMISTRY
SYMPATHOLYTICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES