Nociceptin receptor activation inhibits tachykinergic non adrenergic non cholinergic contraction of guinea pig isolated bronchus

We studied the action of nociceptin (NC) on the atropine-resistant contract ions of the guinea pig isolated bronchus evoked by the electrical field sti mulation (EFS), an effect that is mediated by the activation of excitatory non adrenergic-non cholinergic (eNANC) nerves and the subsequent release of tachykinins. The functional site by which NC acts in this preparation was investigated using few different NC receptor agonists and the newly discove red NC receptor antagonist, [Phe(psi)(1)(CH2-NH)Gly(2)]NC(1-13)NH2 ([F/G]NC (1-13)NH2). NC inhibited in a concentration dependent manner (pEC(50) 7.14; E-max - 87 +/- 3% of control values) EFS induced contractions. NC effect w as mimicked by the NC analogues, NCNH2 and NC(1-13)NH2, but not by NC(1-9)N H2. NC (1 mu M) did not affect the contractile effects of exogenously appli ed neurokinin A (1 mu M) [F/G]NC(1-13)NH2 (10 mu M) completely prevented th e inhibition induced by NC (1 mu M), whereas naloxone (1 mu M) was found in active. Both naloxone and ([F/G]NC(1-13)NH2 were per se inactive on basal r esting tone as well as on the electrically induced contractions. The presen t findings show that NC inhibits the atropine-resistant EFS-induced contrac tion in the guinea pig bronchus by inhibiting eNANC nerves, and suggest the presence of NC receptors, distinct from opioid receptors, on the nerves of the guinea pig bronchus. (C) 1999 Elsevier Science Inc.