Actions of FRC-8653 on smooth muscle cells of the rabbit mesenteric artery.
In ring preparations of the rabbit mesenteric artery, the Ca-contraction, but not the noradrenaline (NA)-contraction, was inhibited by FRC-8653 (10(-9)-10(-5) M) in a concentration-dependent manner, although with a potency 50-100 times weaker than that of nicardipine. The actions of FRC-8653 on Ca-contraction appeared more slowly (over 1 hr) than those of nicardipine. FRC-8653 (up to 10(-5) M) and nicardipine (up to 10(-7) M) did not change the resting membrane potential of smooth muscles. The amplitude of the evoked excitatory junction potential (e.j.p.) was inhibited by FRC-8653, but not by nicardipine, with no alteration in the facilitation process of the e.j.p.s. The inhibition by FRC-8653 of the e.j.p. appeared rapidly and was reversible. FRC-8653 inhibited the membrane depolarization of smooth muscles elicited by ATP, but not by NA or high [K+]o solution. ATP-induced contractions were also inhibited by FRC-8653. The amplitudes of action potentials evoked by current stimuli were decreased by FRC-8653, with no significant change in the electrotonic potentials. Thus, FRC-8653 has properties similar to those of the dihydropyridine Ca-antagonists, but differs from them in that 1) its inhibitory actions on Ca influx appear slowly and 2) sympathetic transmission is inhibited, possibly by inhibition of the postjunctional events for e.j.p. generation.
Nakashima
M
M
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kou
M
M
Hashitani
H
H
Chen
G F
GF
Ono
H
H
Kuriyama
H
H
Suzuki
H
H
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C065927:cilnidipine; D009529:Nicardipine