Nociceptin/orphanin FQ inhibits electrically induced contractions of the human bronchus via NOP receptor activation.
Nociceptin/orphanin FQ (N/OFQ) has been reported to inhibit neurogenic contractions in various tissues, including guinea pig airways. In the present study, we investigated the ability of N/OFQ to affect cholinergic contractions of human bronchi elicited by electrical field stimulation (EFS). Tissues were obtained from 23 patients undergoing surgery for lung cancer. EFS (20 Hz, 320 mA, 1.5 ms, 10 s) was applied five times every 20 min. Contractions induced by EFS were abolished by either TTX (1 microM) or atropine (1 microM) and concentration-dependently (10 nM-1 microM) inhibited by N/OFQ (Emax, 11.5+/-1.8% inhibition). The inhibitory effects of N/OFQ were mimicked by the N/OFQ receptor (NOP) ligand [Arg14, Lys15]N/OFQ which displayed however, higher significant maximal effects (17.7+/-2.9% inhibition, P<0.05). The actions of N/OFQ and [Arg14, Lys15]N/OFQ were not affected by naloxone (1 microM) while prevented by the selective NOP receptor antagonist UFP-101 (10 microM). Moreover, the inhibitory effects of NOP agonists were no longer evident in tissues treated with tertiapin (10 microM), an inhibitor of inward-rectifier potassium channels. In conclusion, the present data demonstrate that N/OFQ inhibited acetylcholine (ACh) release in the human bronchi via NOP receptor activation. This effect may involve stimulation of potassium currents.
Basso
Marco
M
UPRES EA 220-Pharmacology, University of Versailles and UFR Biomédicale des Saint-Péres, 45 rue des Saints Péres, F-75006 Paris, France.
Risse
Paul André
PA
Naline
Emmanuel
E
Calo
Girolamo
G
Guerrini
Remo
R
Regoli
Domenico
D
Advenier
Charles
C
D000368:Aged; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D006801:Humans; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human