Agonist actions of Bay K 8644, a dihydropyridine derivative, on the voltage-dependent calcium influx in smooth muscle cells of the rabbit mesenteric artery.
Actions of methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2- trifluoromethylphenyl)-pyridine-5-carboxylate (Bay K 8644) on the mechanical response evoked in intact and skinned mesenteric artery of the rabbit were investigated. The data were compared to that of nisoldipine, another dihydropyridine derivative Bay K 8644 increased the amplitudes of both the phasic and tonic components of the K+-induced contraction which is due to an increase in the voltage-dependent influx of Ca ion. Bay K 8644 antagonized competitively the actions of nisoldipine (a Ca antagonist) on the tonic but not on the phasic component of the K+-induced contraction. The contractions caused by high concentrations of norepinephrine were enhanced to a greater extent by Bay K 8644 than that evoked by lower concentrations of norepinephrine. Bay K 8644 had no effect on Ca++ extrusion from cells, which was estimated from the change in amplitudes of the norepinephrine-induced contractions in Na+- and Ca++-free solutions. This agent had no effect on the contractile proteins and Ca storage sites, as estimated from the Ca++- or caffeine-induced contraction observed in skinned muscles. The results suggested that Bay K 8644 acts primarily on the voltage-dependent Ca++ channel, presumably the same site at which other dihydropyridine derivatives (Ca antagonists) act, and that the influx of Ca++ is accelerated.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012503:Saponins / Q000494:pharmacology
D012503:Saponins; D002110:Caffeine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine