Nociceptin/orphanin FQ and related peptides reduce the increase in plasma corticosterone elicited in mice by an intracerebroventricular injection.
Nociceptin/orphanin FQ (=N/OFQ), the endogenous ligand of ORL1 receptor (=NOP), has been reported to induce, in rodents, after intracerebroventricular (i.c.v.) administration, anti-stress and anxiolytic effects. We have observed that the handling of mice followed by an i.c.v. injection of saline, induced a marked increase in the plasma corticosterone level (+250%) measured 30 minutes later. When N/OFQ was injected intracerebroventricularly, using a 1 microg dose, the increase in plasma corticosterone was significantly lower than in saline injected mice. N/OFQ(1-13)NH(2), known as a NOP receptor agonist, at the same 1 microg dose, also induced a lesser increase in plasma corticosterone level than a saline i.c.v. injection. The pseudopeptide [Phe(1)-psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)NH(2), defined either as an agonist or an antagonist of NOP receptor, at the 0.1 microg dose, behaved in a similar manner as N/OFQ, by decreasing the plasma corticosterone level. Finally, [Nphe(1)]N/OFQ(1-13)NH(2), although presumed to be a selective NOP receptor antagonist, also decreased the corticosterone level at the 0.1 microg dose. These observations suggest the implication of N/OFQ in the regulation of response to stress, through an action on the hypothalamo-pituitary-adrenocortical axis. Moreover, they evidence a similar effect of N/OFQ and N/OFQ(1-13)NH(2), but also of two other related peptides displaying antagonist properties on NOP receptors. These data suggest that several subtypes of N/OFQ receptors could exist.
Le Cudennec
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C.N.R.S. - U.M.R. 6036, I.F.R.M.P. no. 23, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183, Rouen, France.
Naudin
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B
Do Rego
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JC
Costentin
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D000818:Animals; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006234:Handling, Psychological; D007276:Injections, Intraventricular / Q000009:adverse effects*; D008297:Male; D051379:Mice; D018847:Opioid Peptides / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D003345:Corticosterone; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722287:Oprl1 protein, mouse