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

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 μ‐receptor agonist, H‐Tyr‐d‐Arg‐Phe‐Lys‐NH2 (DALDA, 0.1–1 mg kg−1, i.v.) or the α2‐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 μ‐opioid receptors or α2‐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.