Allosteric Interactions at L-type Calcium Channels Between FPL 641 76 and the Enantiomers of the Dihydropyridine

Functional interactions between the enantiomers of the dihy-dropyndine 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluorom-ethyl)-phenylj-3-pyridine carboxylic acid methyl ester (Bay K 8644) and the benzoylpyrrole methyl 2,5-dimethyl-4-[2(phenyl-methyl)benzoyl]-H-pyrrole-3-carboxylate (FPL 64176) were in-vestigated on L-type Ca channels in guinea pig ileal longi-tudinal smooth muscle. The effects of these drugs, when applied individually, were as described in earlier studies. Forinstance,both (-)-(S)-Bay K 8644 and FPL 641 76 caused concentration-dependent contraction, which is consistent with Ca channel activation, whereas (+)-(R)-Bay K 8644 gave concentration-dependent relaxation, which is consistent with Ca channel inhibition. The activities of the different drugs were dependent on the extracellular levels of KCI. When ap-plied in combination, however, the responses evoked were not those predicted from the effects of the drugs applied individu-ally. Contractions produced by FPL 641 76 (25 nM to 1 M) were abolished in the presence of 1 00 nM (-)-(S)-Bay K 8644 but were potentiated by 1 0 to 1 50 nM (+)-(R-Bay K 8644 an