RT Journal Article
SR Electronic
T1 The relationship between the binding site of [3H]-d-cis-diltiazem and that of other non-dihydropyridine calcium entry blockers in cardiac sarcolemma.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 175
OP 179
VO 31
IS 2
A1 J L Balwierczak
A1 C L Johnson
A1 A Schwartz
YR 1987
UL http://molpharm.aspetjournals.org/content/31/2/175.abstract
AB [3H]-d-cis-Diltiazem binds to canine cardiac sarcolemma in a specific, saturable, and reversible manner with a KD = 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 nM concentrations. This inhibition was determined from saturation binding data to be due to a change in affinity of the radioligand, suggesting a competitive interaction between the three drugs. However, in dissociation experiments, both bepridil and verapamil increased the dissociation rate of the radioligand. This effect is uncharacteristic of competitive inhibitors and suggests that bepridil and verapamil regulate [3H]-d-cis-diltiazem binding in a negative allosteric fashion through their own distinct binding sites.