Potential-dependent interactions of nitrendipine and related 1,4-dihydropyridines in functional smooth muscle preparations.
Interaction of nitrendipine and other Ca2+ channel antagonists including nifedipine, diltiazem, and D600 with intestinal smooth muscle was shown to depend on membrane potential. In the absence of extracellular Ca2+, guinea pig ileal longitudinal muscle does not contract and can be incubated at various K+ concentrations in the presence or absence of antagonist. Preincubation with elevated K+ prior to admission of Ca2+ and challenge with K+ to a total of 100 mM increased the activity of the antagonist. The IC50 for nitrendipine incubated in the presence of 5 mM K+ was 5.36 X 10(-9) M and in the presence of 40 mM K+ was 0.53 X 10(-9) M. Other 1,4-dihydropyridines showed similar potency shifts.
Triggle
D J
DJ
School of Pharmacy, State University of New York, Buffalo 14260.
Hawthorn
M
M
Zheng
W
W
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology
D004095:Dihydropyridines; D009568:Nitrendipine; D011188:Potassium; D002118:Calcium