MOLECULAR PHARMACOLOGY. 31:175-179 The Relationship Between the Binding Site of [3H]-.d-cis- Diltiazem and that of Other Non-Dihydropyridine Calcium Entry Blockers in Cardiac Sarcolemma

[3H}-d-cis-Diltiazem binds to canine cardiac sarcolemma in a specific, saturable, and reversible manner with a K0 = 58.0 ± 9.5 nM and a receptor site density (maximum binding) of 2.19 ± 0.24 pmol/mg of protein. Bepridil and verapamil, Ca2 channel inhibitors, can completely inhibit this binding at n concentra-tions. This inhibition was determined from saturation binding data to be due to a change in affinity of the radioligand, sug-gesting a competitive interaction between the three drugs. How-ever, in dissociation experiments, both bepridil and verapamil increased the dissociation rate of the radioligand. This effect is uncharacteristic of competitive inhibitors and suggests that be-pndil and verapamil regulate [3H]-d-cis-diltiazem binding in a negative allosteric fashion through their own distinct binding sites. The activation of cardiac and smooth muscle contractio