Nociceptin inhibits cough in the guinea-pig by activation of ORL(1) receptors |
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Authors: | McLeod R L Parra L E Mutter J C Erickson C H Carey G J Tulshian D B Fawzi A B Smith-Torhan A Egan R W Cuss F M Hey J A |
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Affiliation: | Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey, NJ 07033-0539, USA. robbie.mcleod@spcorp.com |
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Abstract: | We studied the central and peripheral antitussive effect of ORL(1) receptor activation with nociceptin/orphanin FQ in conscious guinea-pigs. In guinea-pig cough studies, nociceptin/orphanin FQ (10, 30, and 90 microg) given directly into the CNS by an intracerebroventricular (i.c.v.) route inhibited cough elicited by capsaicin exposure by approximately 23, 29 and 52%, respectively. The antitussive activity of nociceptin/orphanin FQ (90 microg, i.c.v.) was blocked by the selective ORL(1) antagonist [Phe(1)gamma(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) (180 microg, i.c.v.) and J113397 (10 mg kg(-1), i.p.) but not by the opioid antagonist, naltrexone (3 mg kg(-1), i.p.). Furthermore, intravenous (i.v.) nociceptin/orphanin FQ (1.0 and 3.0 mg kg(-1)) also inhibited cough approximately by 25 and 42%, respectively. These findings indicate that selective ORL(1) agonists display the potential to inhibit cough by both a central and peripheral mechanism, and potentially represent a novel therapeutic approach for the treatment of cough. |
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