Relationship between the binding sites of (/sup 3/H)d-cis-diltiazem and other calcium entry blockers in canine cardiac sarcolemma

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5453440

Balwierczak, J L; Johnson, C L; Schwartz, A

Saturable, reversible and stereospecific binding of (/sup 3/H)d-cis-diltiazem ((/sup 3/H)-DTZ) was shown in purified canine cardiac sarcolemma. Saturation and inhibition binding at 25/sup 0/C in 0.05 M Tris-Maleate buffer, pH 7.75, yielded K/sub D/ and B/sub max/ values for (/sup 3/H)-DTZ of 54.6 +/- 5.0 nM and 2.31 +/- .42 pmol/mg, respectively. Binding was completely inhibited by the calcium channel blockers, verapamil and bepridil and by calcium itself. The K/sub i/ values for verapamil, bepridil and calcium were 28.9 nM, 289 nM and 300 ..mu..M, respectively. The inhibition of (/sup 3/H)-DTZ binding by bepridil appears to be competitive in nature, since in saturation experiments the effects of 300 nM and 600 nM bepridil were to increase the K/sub D/ of (/sup 3/H)-DTZ to 95.6 nM and 152 nM, respectively, compared to the control K/sub D/ of 54.6 nM. No significant effect was seen on the B/sub max/ of binding. Nitrendipine caused only a slight (approx. 20%) increase in binding at subnanomolar concentrations, with inhibition of binding even up to concentrations of 0.5 ..mu..M. The relationship between the binding sites of (/sup 3/H)-DTZ and other classes of calcium entry blockers, viz, verapamil, bepridil, and dihydropyridines appears to be complex.

• Research Organization: Univ. of Cincinnati, OH
• OSTI ID: 5453440
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
CALCIUM
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
DOGS
DRUGS
ELEMENTS
HEART
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
METALS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RECEPTORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASODILATORS
VERTEBRATES