RT Journal Article
SR Electronic
T1 Mechanism of Relaxant Effect of Clonidine in Isolated Bovine Tracheal Smooth Muscle
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 681
OP 687
VO 286
IS 2
A1 Masashi Arimitsu
A1 Minori Mitsui-Saito
A1 Koichi Sato
A1 Hiroshi Ozaki
A1 Yoshihisa Koga
A1 Hideaki Karaki
YR 1998
UL http://jpet.aspetjournals.org/content/286/2/681.abstract
AB 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 μM carbachol (CCh) but not in 72.7 mM KCl-induced contraction. The relaxation in CCh-contracted BTSM was inhibited by yohimbine (1 μM) and idazoxan (10 and 30 μM) but not by tetrodotoxin, indomethacin and other adrenoceptor antagonists. Oxymetazoline (0.1–100 μM) and phentolamine (0.1–100 μM) caused concentration-dependent relaxation, which was attenuated by idazoxan (10 μM). Norepinephrine (0.1–100 μM) produced concentration-dependent relaxation, which was completely abolished by propranolol (10 μM) but not by yohimbine (1 μM). 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 μM) 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 I1receptors. The American Society for Pharmacology and Experimental Therapeutics