Nociceptin inhibits cough in the guinea-pig by activation of ORL1 receptors

摘要

We studied the central and peripheral antitussive effect of ORL1 receptor activation with nociceptin/orphanin FQ in conscious guinea-pigs. In guinea-pig cough studies, nociceptin/orphanin FQ (10, 30, and 90 μg) 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 μg, i.c.v.) was blocked by the selective ORL1 antagonist [Phe1γ(CH2-NH)Gly2]nociceptin-(1-13)-NH2 (180 μg, 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 ORL1 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.