Mechanism of relaxant effect of clonidine in isolated bovine tracheal smooth muscle.
The relaxant effect of clonidine and the possible involvement of imidazoline I1 receptors in bovine tracheal smooth muscle (BTSM) were examined. Clonidine caused concentration-dependent significant relaxation in BTSM precontracted with 0.1 or 1 microM carbachol (CCh) but not in 72.7 mM KCl-induced contraction. The relaxation in CCh-contracted BTSM was inhibited by yohimbine (1 microM) and idazoxan (10 and 30 microM) but not by tetrodotoxin, indomethacin and other adrenoceptor antagonists. Oxymetazoline (0.1-100 microM) and phentolamine (0.1-100 microM) caused concentration-dependent relaxation, which was attenuated by idazoxan (10 microM). Norepinephrine (0.1-100 microM) produced concentration-dependent relaxation, which was completely abolished by propranolol (10 microM) but not by yohimbine (1 microM). In fura-PE3/AM-loaded BTSM, CCh and 72.7 mM KCl increased intracellular calcium concentration ([Ca++]i) followed by contraction. The high K+-induced increase in [Ca++]i was not affected by clonidine. In CCh-stimulated BTSM, clonidine decreased [Ca++]i and muscle force in parallel, whereas verapamil decreased [Ca++]i more strongly than muscle force. Clonidine (100 microM) inhibited the transient increase in [Ca++]i induced by CCh but not by caffeine (20 mM) in Ca++-free solution. Clonidine did not change the cAMP content in the presence of either 72.7 mM KCl or CCh. These results indicate that clonidine relaxes CCh-stimulated BTSM through the inhibition of CCh-induced increases in Ca++-influx, Ca++-release and intracellular signal transduction probably via imidazoline I1 receptors.
Arimitsu
M
M
Department of Anesthesiology, Kinki University School of Medicine, Osaka, Japan.
Mitsui-Saito
M
M
Sato
K
K
Ozaki
H
H
Koga
Y
Y
Karaki
H
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D003000:Clonidine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010109:Oxymetazoline / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010109:Oxymetazoline; D000242:Cyclic AMP; D003000:Clonidine; D002118:Calcium; D010646:Phentolamine