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Characteristics of the phenylalkylamine binding site in canine cardiac sarcolemmal preparations

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5497490
The phenylalkylamine binding site in canine cardiac sarcolemma was investigated using /sup 3/H(S)-desmethoxyverapamil (/sup 3/H(S)-D888) as labeled ligand. Radioligand binding experiments were carried out in a medium containing 1 mM EGTA and 10 mM Hepes-Na buffer, pH 7.4 at 20/sup 0/C. In 1 ml buffer, 75-100 ..mu..g protein were incubated for 1 hour and the bound /sup 3/H(S)-D888 was separated by rapid filtration through GF/C filters. A single high affinity binding site was identified for /sup 3/H(S)-D888 both by saturation and competition binding experiments. Several phenylalkylamine derivatives such as (-)D600, (+)D600, verapamil and (R)-D888 completely inhibited /sup 3/H(S)-D888 binding. The order of potency: (S)-D888 GAMMA (-)D600 > verapamil > (R)-D888 = (+)D600. In contrast to this, ronipamil produced only a 70% inhibition. /sup 3/H(S)-D888 binding was also inhibited by Ca/sup + +/ and by Mg/sup + +/. These data suggest the presence of a saturable, reversible and stereospecific phenylalkylamine binding site in canine cardiac sarcolemmal preparations which may be a receptor for the phenylalkylamine Ca/sup + +/ channel inhibitors.
Research Organization:
Univ. of Cincinnati College of Medicine, OH
OSTI ID:
5497490
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