AGONIST ACTIONS OF BAY K-8644, A DIHYDROPYRIDINE DERIVATIVE, ON THE VOLTAGE-DEPENDENT CALCIUM INFLUX IN SMOOTH-MUSCLE CELLS OF THE RABBIT MESENTERIC-ARTERY

Abstract

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 of which is due to an increase in the voltage-dependent influx of Ca2+. 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 Ca2+ extrusion from cells, which was estimated from the change in amplitudes of the norepinephrine-induced contractions in Na+- and Ca2+-free solutions. This agent had no effect on the contractile proteins and Ca storage sites, as estimated from the Ca2+- or caffeine-induced contraction observed in skinned muscles. Apparently, Bay K 8644 acts primarily on the voltage-dependent Ca2+ channel, presumably the same site at which other dihydropyridine derivatives (Ca antagonists) act, and the influx of Ca2+ is accelerated.