Analysis of the properties of binding of calcium-channel activators and inhibitors to dihydropyridine receptors in chick heart membranes.

The interaction of 1,4-dihydropyridine derivatives with their receptors on voltage-dependent calcium channels in cardiac membranes was studied to determine if there are basic differences in the binding properties of ligands that cause inhibition or activation of calcium channels. The binding characteristics of 6 pure stereoisomers, (-) and (+)202-791, (-) and (+)Bay k 8644, (-) and (+)PN 200-110, as well as racemic Bay k 8644 and nitrendipine, were compared. Competition studies using the cold ligands and 3 different radiolabelled dihydropyridines, (+)[3H]PN 200-110, (+/-)[3H]nitrendipine, and (+/-)[3H]Bay k 8644, showed that, for each combination tested, the labelled dihydropyridine could be displaced by the cold dihydropyridine. The binding reactions were markedly affected by temperature. The Kd values for most compounds were significantly higher (5-19 times) at 0 degrees than at 37 degrees C. In contrast, the affinity of (+)PN 200-110 was similar at 0 degrees and 37 degrees C, but slightly higher at 25 ...