PT - JOURNAL ARTICLE AU - E Tagaya AU - J Tamaoki AU - A Chiyotani AU - K Konno TI - Stimulation of opioid mu-receptors potentiates beta adrenoceptor-mediated relaxation of canine airway smooth muscle. DP - 1995 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1288--1292 VI - 275 IP - 3 4099 - http://jpet.aspetjournals.org/content/275/3/1288.short 4100 - http://jpet.aspetjournals.org/content/275/3/1288.full SO - J Pharmacol Exp Ther1995 Dec 01; 275 AB - To elucidate the effect of an opioid on airway smooth muscle relaxant responses and its mechanism of action, we studied canine bronchial segments under isometric conditions in vitro. Addition of the opioid mu-receptor-specific agonist DAMGO (10(-5) M) or Tyr-D-Arg-phe-Lys-NH2 (10(-5) M) did not alter the resting tension or the contractile responses to Ach but augmented the relaxation induced by isoproterenol: the concentrations of isoproterenol required to produce a half-maximal effect were decreased from 1.9 +/- 0.6 x 10(-6) to 3.1 +/- 1.0 x 10(-7) M (P < .01) by DAMGO and from 2.1 +/- 0.4 x 10(-6) M to 4.3 +/- 0.7 x 10(-7) M (P < .01), by Tyr-D-Arg-phe-Lys-NH2. This effect of DAMGO was concentration-dependent and was abolished by naloxone or Cys2, Tyr3, Orn5, Pen7-amide, a mu-receptor antagonist. DAMGO likewise caused a leftward displacement of concentration-response curves for forskolin but was without effect on those for 3-isobutyl-3-methylxanthine and 8-bromo-cAMP. Also, DAMGO did not affect the relaxant responses to verapamil, nitroprusside or 8-bromo-cGMP. Incubation of bronchial smooth muscle with DAMGO (10(-5) M) potentiated the intracellular accumulation of cAMP induced by isoproterenol (10(-6) M) from 258 +/- 22 pmol/g tissue wt. to 420 +/- 27 pmol/g tissue wt. (P < .01), an effect that was abolished by naloxone. These results suggest that stimulation of opioid mu-receptors specifically augments beta adrenoceptor-mediated bronchodilation probably by acting at the site proximal to adenylate cyclase in the cAMP-dependent pathway.