Nitrendipine potentiates Bay k 8644-induced contraction of isolated porcine coronary artery: evidence for functionally distinct dihydropyridine receptor subtypes.
Bay k 8644 and nitrendipine, dihydropyridines classified as calcium channel agonist and antagonist, respectively, produced concentration-dependent biphasic responses (contraction and relaxation) in porcine coronary artery rings. Nitrendipine relaxed rings (IC50 = 60 nM) that were contracted with 100 nM Bay k 8644. Pretreatment of rings with 60 nM nitrendipine caused paradoxical potentiation of Bay k 8644-induced contraction. The data are consistent with a model that consists of two functionally-distinct dihydropyridine "receptors" with which Bay k 8644 and nitrendipine interact as partial agonists. We propose that these excitatory and inhibitory dihydropyridine receptor subtypes mediate contraction and relaxation, respectively, by dihydropyridines.
Dube
G P
GP
Baik
Y H
YH
Vaghy
P L
PL
Schwartz
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D015220:Calcium Channels; D003331:Coronary Vessels / Q000187:drug effects; D004357:Drug Synergism; D066298:In Vitro Techniques; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013552:Swine
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D009543:Nifedipine