Effects of morphine, H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and B-HT920 on non-cholinergic nerve-mediated bronchoconstriction in pithed guinea-pigs

Abstract

1. Electrical stimulation (1 ms, 5 Hz, 80 V) for 5 or 15 s at the level of C4-T1 in the spinal canal of artificially respired pithed guinea-pigs (which had received intravenously (i.v.) (+)-tubocurarine chloride 2 mg kg-1, atropine sulphate 2 mg kg-1 and pentolinium tartrate 5 mg kg-1) caused constriction of airways, indicated by increased insufflation pressure. 2. This non-cholinergic constriction was inhibited by morphine (1-3 mg kg-1, i.v.), the peripherally acting mu-receptor agonist, H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA, 0.1-1 mg kg-1, i.v.) or the alpha 2-adrenoceptor agonist B-HT920 (1-3 mg kg-1, i.v.). 3. The effects of either morphine (3 mg kg-1, i.v.) or DALDA (1 mg kg-1, i.v.) were inhibited by naloxone (3 mg kg-1, i.v.). Idazoxan (3 mg kg-1, i.v.) inhibited the anti-constrictor effect of B-HT920 (3 mg kg-1, i.v.), but not that of DALDA (0.1 mg kg-1, i.v.). 4. Thus activation of peripheral mu-opioid receptors or alpha 2-adrenoceptors inhibits airways constriction induced by non-cholinergic nerve stimulation in the pithed guinea-pig. This preparation therefore provides a further method for the in vivo examination of the effects of drugs on non-cholinergic tracheobronchial constrictor nerve function.