Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle.
We examined the relaxant effects of N-acetylprocainamide, the major hepatic metabolite of procainamide, on bovine tracheal smooth muscle, focusing on the possible involvement of K+ channels. N-acetylprocainamide produced a concentration-dependent and full inhibition of the tension development elicited by methacholine (0.3 or 1 microM). The potency of N-acetylprocainamide in diminishing methacholine-elicited tension development was one-half of that of procainamide. By comparison, N-acetylprocainamide inhibited high-K+ (40 mM)-induced contraction more potently than procainamide though both inhibitions were largely reduced when compared to those against methacholine-induced contraction. Iberiotoxin (30 nM), Ba(2+) (1 mM) or a combination of both agents significantly attenuated the relaxant effect of N-acetylprocainamide on methacholine-induced contraction, whereas apamin (100 nM), 4-aminopyridine (300 microM), and glibenclamide (10 microM) did not affect it. These results suggest that N-acetylprocainamide, similar to procainamide, elicits tracheal smooth muscle relaxation mainly through the activation of plasma membrane K+ channels.
Nakahara
T
T
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. nakaharat@pharm.kitasato-u.ac.jp
Moriuchi
H
H
Tanaka
Y
Y
Yunoki
M
M
Kubota
Y
Y
Sakamato
K
K
Shigenobu
K
K
Ishii
K
K
D000120:Acecainide / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011342:Procainamide / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D016210:Methacholine Chloride; D001464:Barium; C064719:iberiotoxin; D000120:Acecainide; D011342:Procainamide; D011188:Potassium