Relationship between the binding sites of (/sup 3/H)d-cis-diltiazem and other calcium entry blockers in canine cardiac sarcolemma
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-; TRN: 86-026598
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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TRACER TECHNIQUES
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ALKALINE EARTH METALS
ANIMALS
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CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
DRUGS
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550201* - Biochemistry- Tracer Techniques