ISSN:
1435-1803
Keywords:
desmethoxyverapamil
;
phenylalkylamine
;
binding sites
;
calcium antagonists
;
canine cardiac
;
sarcolemma
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary We have investigated the phenylalkylamine binding site in canine cardiac sarcolemmal preparations using (−)-[3H]-desmethoxyverapamil as the labeled ligand. Radioligand binding experiments were carried out in 10 mM Hepes (Na+) buffer and 1 mM EGTA, at pH 7.4 and 20°C. A single high affinity binding site for (−)-[3H]-desmethoxyverapamil was identified both by saturation and competition binding experiments. Several phenylalkylamine derivatives such as (−)-D600, (+)-D600, verapamil and (+)-desmethoxyverapamil completely inhibited (−)-[3H]-desmethoxyverapamil binding with the following order of potency: (−)-desmethoxyverapamil〉(−)-D600〉verapamil〉(+)-desmethoxyverapamil=(+)-D600. In contrast to this, ronipamil, a new long acting phenylalkylamine derivative, produced only a 70% inhibition. Diltiazem also completely inhibited (−)-[3H]-desmethoxyverapamil binding to canine cardiac sarcolemma while nifedipine displaced only 70% of binding. (−)-[3H)-desmethoxyverapamil binding was also inhibited by Ca++ and Mg++. These data suggest the presence of a saturable, reversible and stereoselective phenylalkylamine binding site in canine cardiac sarcolemmal preparations which may be a receptor for the phenylalkylamine Ca++ channel inhibitors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02005822
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