Abstract

The binding of the Ca 2+-channel blocker d- cis-[ 3H]diltiazem to guinea pig skeletal muscle microsomes is temperature-dependent. At 2°C the K D is 39 nM and B max is 11 pmol/mg protein. The binding is fully reversible ( K −1 = 0.02 min −1). The binding sites discriminate between the diastereoisomers 1- and d- cis-diltiazem, recognize verapamil, gallopamil and tiapamil, and are sensitive to La 3+-inhibition. At 30°C the K D is 37 nM and the B max is 2.9 pmol/mg protein. D- cis-diltiazem-labelling is regulated by the 1,4-dihydropyridine Ca 2+-channel blockers and a novel Ca 2+-channel activator in a temperature-dependent manner. At 30°C an enhancement of d- cis-diltiazem binding by the channel blockers is observed. This is attributed to a B max increase. EC 50-values for enhancement and the maximal enhancement differ for the individual 1,4-dihydropyridines. At 2°C 1,4-dihydropyridines inhibit d- cis-[ 3H]diltiazem binding. This is attributed to a B max decrease. We have directly labelled one of the drug receptor sites within the Ca 2+-channel which can allosterically interact with the 1,4-dihydropyridine binding sites.

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