MECHANISM OF RELAXANT EFFECT OF CLONIDINE IN ISOLATED BOVINE TRACHEALSMOOTH-MUSCLE

The relaxant effect of clonidine and the possible involvement of imida zoline I, receptors in bovine tracheal smooth muscle (BTSM) were exami ned. Clonidine caused concentration-dependent significant relaxation i n BTSM precontracted with 0.1 or 1 mu M carbachol (CCh) but not in 72. 7 mM KCl-induced contraction. The relaxation in CCh-contracted BTSM wa s inhibited by yohimbine (1 mu M) and idazoxan (10 and 30 mu M) but no t by tetrodotoxin, indomethacin and other adrenoceptor antagonists. Ox ymetazoline (0.1-100 mu M) and phentolamine (0.1100 mu M) caused conce ntration-dependent relaxation, which was attenuated by idazoxan (10 mu M). Norepinephrine (0.1-100 mu M) produced concentration-dependent re laxation, which was completely abolished by propranolol (10 mu M) but not by yohimbine (1 mu M). In fura-PE3/AM-loaded BTSM, CCh and 72.7 mM KCI increased intracellular calcium concentration ([Ca++](i)) followe d by contraction. The high K+-induced increase in [Ca++](i) was not af fected by clonidine. In CCh-stimutated BTSM, clonidine decreased [Ca+](i) and muscle force in parallel, whereas verapamil decreased [Ca++]( i) more strongly than muscle force. Clonidine (100 mu M) inhibited the transient increase in [Ca++](i) induced by CCh but not by caffeine (2 0 mM) in Ca++ free solution. Clonidine did not change the cAMP content in the presence of either 72.7 mM KCI or CCh. These results indicate that clonidine relaxes CCh-stimulated BTSM through the inhibition of C Ch-induced increases in Ca++-influx, Ca++-release and intracellular si gnal transduction probably via imidazoline I, receptors.