Opioid receptor like 1 (ORL1) receptor is a novel member of the opioid receptor family, which was not bound by any of the typical opioid receptor ligands but bound by the recently discovered nociceptin (also termed orphanin FQ) with high af

[Phe1ψ(CH2-NH) Gly2 nociceptin-(1-13)-NH2, a pseudopeptide analog of nociceptin, was originally seen as an antagonist of nociceptin receptors. In the present study, it was observed that intracerebroventricular (i. c. v.) injection of this pseudopeptide (1, 5, 10μg) significantly decreased the tail-flick latency of rats, indicating a hyperalgesic effect, while intrathecal (i. t.) injection of it (1, 2.5, 10μg) dramatically increased the tail-flick latency, indicating an analgesic effect. This strengthened the in vivo evidence that [Phe1ψ(CH2-NH) Gly2] nociceptin-1-13-NH might be an agonist of nociceptin receptors.

Orphanin FQ (also known as nociceptin) is a 17-amino-acid peptide which acts as a potent endogenous agonist of the orphan opioid receptor-like (ORL1) receptor. Endomorphin-1, a 4-amino-acid peptide discovered recently, is a potent and selective endogenous agonist for the m-opiate receptor. In the present study, the effect of OFQ orrand endomorphin-1 on the response to noxious thermal stimuli was observed using the tail-flick test in rats. Intracerebroventricular (i. c. v.) administration of OFQ (1,5μg) could shorten tail-flick latency; In contrast, intrathecal (i. t.) administration of OFQ (1, 2 or 10μg) could increase the latency; i. c. v. (1, 2, 5μg) or i. t. (0.2, 2, 5μg) administration of endomorphin-1 dose-dependently increased the latency, indicating an analgesic effect. Furthermore, OFQ (0.1-5μg) when intraventricularly injected together with endomorphin-1 (5μg), could dose-dependently reverse the analgesia induced by the latter. On the contrary, OFQ (1μg) intrathecally injected together with endomorphin-1 (0.2μg) could further increase the tail-flick latency. The results showed that OFQ at the supraspinal level produces hyperalgesia and is antagonistic to endomorphin-1, while at the spinal level it produces analgesia and is synergic with endomorphin-1. Different interaction mechanism between OFQ and endomorphin-1 in the brain and the spinal cord is thus suggested. © 1999 Elsevier Science B. V. All rights reserved.