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 contractions of the guinea pig isolated bronchus evoked by the electrical field stimulation (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 discovered NC receptor antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2). NC inhibited in a concentration dependent manner (pEC50 7.14; Em - 87 +/- 3% of control values) EFS induced contractions. NC effect was mimicked by the NC analogues, NCNH2 and NC(1-13)NH2, but not by NC(1-9)NH2. NC (1 microM) did not affect the contractile effects of exogenously applied neurokinin A (1 microM). [F/G]NC(1-13)NH2 (10 microM) completely prevented the inhibition induced by NC (1 microM), whereas naloxone (1 microM) was found inactive. Both naloxone and ([F/G]NC(1-13)NH2 were per se inactive on basal resting tone as well as on the electrically induced contractions. The present findings show that NC inhibits the atropine-resistant EFS-induced contraction 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.
Rizzi
A
A
Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
Calò
G
G
Trevisani
M
M
Tognetto
M
M
Fabbri
L
L
Mapp
C
C
Guerrini
R
R
Salvadori
S
S
Regoli
D
D
Geppetti
P
P
D000818:Animals; D001980:Bronchi / Q000294:innervation; D016084:Bronchoconstriction; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D018039:Receptors, Tachykinin / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D000094942:Nociceptin Receptor
D011957:Receptors, Opioid; D018039:Receptors, Tachykinin; D013373:Substance P; D015288:Neurokinin A; D000094942:Nociceptin Receptor