Effects of cyproheptadine on [3H]-d-cis-diltiazem binding sites in cardiac sarcolemmal membranes of rats.

The characteristics of [3H]-d-cis-diltiazem binding sites in cardiac sarcolemmal membrane of rats and effects of diltiazem and cyproheptadine (Cyp) on these binding sites were studied. [3H]-d-cis-diltiazem, a benzothiazepine calcium antagonist, was shown to be bound to crude cardiac sarcolemmal membrane of rats in a specific and saturable manner with a KD = 84 nmol.L-1 and a receptor site density (maximum binding) of 0.279 pmol.mg protein-1. Diltiazem and Cyp, an antiserotonin-antihistaminic agent with calcium channel blocker activity, was found to completely inhibit the binding with Ki values of 102 nmol.L-1 and 5.5 mumol.L-1, respectively. The results demonstrate the existence of [3H]-d-cis-diltiazem binding sites in cardiac sarcolemmal membrane of rats and also suggest that the calcium channel blocker activity of Cyp on cardiac cells may be related, at least in part, to its binding to the [3H]-d-cis-diltiazem binding sites in cardiac sarcolemmal membranes.