Involvement of K(+) channel in procainamide-induced relaxation of bovine tracheal smooth muscle.
The relaxant effect of procainamide, a class Ia antiarrhythmic agent, was examined in bovine tracheal smooth muscle. Procainamide produced concentration-dependent decreases in tension and full relaxation in the preparations contracted with methacholine (0.3 microM). By comparison, in preparations contracted with 40 mM K(+), procainamide had only slight relaxant effects. The relaxant effects of cromakalim and salbutamol on 40 mM K(+)-contracted preparations were significantly (P<0.01) smaller than those on 0.3 microM methacholine-contracted ones. On the other hand, the concentration-response relationships for quinidine, lidocaine, mexiletine and propafenone were not so dramatically different between 0.3 microM methacholine- and 40 mM K(+)-contracted preparations. Tetraethylammonium (300 microM), iberiotoxin (30 nM) and Ba(2+) (1 mM) significantly (P<0.05) attenuated the relaxant effects of procainamide on methacholine-induced contractions, whereas apamin (100 nM), 4-aminopyridine (300 microM), and glibenclamide (10 microM) did not affect them. The inhibitory effect of a combination of iberiotoxin and Ba(2+) was greater than that of iberiotoxin or Ba(2+) alone (P<0.01). These results suggest that the activation of at least two types of K(+) (maxi-K(+) and inward rectifier K(+)) channels contributes to the procainamide-induced relaxation of bovine tracheal smooth muscle.
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
Yunoki
M
M
Kubota
Y
Y
Tanaka
Y
Y
Sakamato
K
K
Shigenobu
K
K
Ishii
K
K
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002417:Cattle; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology; D008801:Mexiletine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011342:Procainamide / Q000494:pharmacology*; D011405:Propafenone / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D015221:Potassium Channels; D016210:Methacholine Chloride; D008801:Mexiletine; D011405:Propafenone; D011802:Quinidine; D011342:Procainamide; D000420:Albuterol; D011188:Potassium