Usowicz M M, Gigg M, Jones L M, Cheung C W, Hartley S A
Dept. of Pharmacology, University of Bristol, United Kingdom.
J Pharmacol Exp Ther. 1995 Nov;275(2):638-45.
Functional interactions between the enantiomers of the dihydropyridine 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridi ne carboxylic acid methyl ester (Bay K 8644) and the benzoylpyrrole methyl 2,5-dimethyl-4-[2(phenylmethyl)benzoyl]-H-pyrrole-3-carboxylate (FPL 64176) were investigated on L-type Ca++ channels in guinea pig ileal longitudinal smooth muscle. The effects of these drugs, when applied individually, were as described in earlier studies. For instance, both (-)-(S)-Bay K 8644 and FPL 64176 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 applied in combination, however, the responses evoked were not those predicted from the effects of the drugs applied individually. Contractions produced by FPL 64176 (25 nM to 1 microM) were abolished in the presence of 100 nM (-)-(S)-Bay K 8644 but were potentiated by 10 to 150 nM (+)-(R)-Bay K 8644 and inhibited by 1 microM (+)-(R)-Bay K 8644. Conversely, contractile responses to (-)-(S)-Bay K 8644 were abolished by 100 nM FPL 64176. In the presence of 1 microM FPL 64176, however, (-)-(S)-Bay K 8644 gave concentration-dependent relaxation of the muscle, which is consistent with Ca++ channel inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
在豚鼠回肠纵行平滑肌的L型钙离子通道上，研究了二氢吡啶1,4 - 二氢 - 2,6 - 二甲基 - 5 - 硝基 - 4 - [2 - (三氟甲基) - 苯基] - 3 - 吡啶羧酸甲酯（Bay K 8644）对映体与苯甲酰吡咯甲基2,5 - 二甲基 - 4 - [2 - (苯甲基)苯甲酰基] - H - 吡咯 - 3 - 羧酸酯（FPL 64176）之间的功能相互作用。这些药物单独应用时的作用如早期研究所描述。例如，(-)-(S)-Bay K 8644和FPL 64176均引起浓度依赖性收缩，这与钙离子通道激活一致，而(+)-(R)-Bay K 8644则产生浓度依赖性舒张，这与钙离子通道抑制一致。不同药物的活性取决于细胞外氯化钾水平。然而，当联合应用时，所诱发的反应并非单独应用药物时所预测的那样。FPL 64176（25 nM至1 microM）产生的收缩在100 nM (-)-(S)-Bay K 8644存在时被消除，但在10至150 nM (+)-(R)-Bay K 8644存在时增强，而在1 microM (+)-(R)-Bay K 8644存在时受到抑制。相反，100 nM FPL 64176可消除对(-)-(S)-Bay K 8644的收缩反应。然而，在1 microM FPL 64176存在时，(-)-(S)-Bay K 8644使肌肉产生浓度依赖性舒张，这与钙离子通道抑制一致。（摘要截短于25
