Disease relevance of Oprl1

• Whereas an AS ODN probe directed against the KOR3/ORL-1 clone produced small (36%), but significant reductions in 2DG-induced hyperphagia, an AS ODN probe directed against the DOR-1 clone was ineffective [1].
• We conclude that spinal ORL-1 receptors can modulate neurogenic inflammation by suppressing the GABAergic neuronal activity in the dorsal horn that is responsible for generating DRRs [2].
• Relationship of pronociceptin/orphanin FQ and the nociceptin receptor ORL1 with substance P and calcitonin gene-related peptide expression in dorsal root ganglion of the rat [3].
• We conclude that renal opioid receptor-like 1 receptor stimulation in normal and congestive heart failure rats produces aquaresis by a direct renal effect, via aquaporin-2 downregulation, through a mechanism not involving inhibition of vasopressin type-2 receptor-mediated cAMP production [4].
• 1 Stimulation of the opioid receptor-like1 (ORL-1) receptor by nociceptin (NC) produces hyperalgesia and reverses the antinociceptive effects induced by opioids [5].

Psychiatry related information on Oprl1

• An endogenous ligand of opioid receptor like 1, nociceptin is reported to inhibit light-induced phase shifts in locomotor activity rhythm [6].
• 4. The anti-opioid effect of OFQ in rat brain and the high level of expression of LC132/ORL, receptor in the locus coeruleus indicated a possible role of OFQ in the precipitation of opiate withdrawal symptoms [7].
• Pharmacological characterization of the nociceptin receptor which mediates reduction of alcohol drinking in rats [8].
• These findings provide further evidence that selective agonists at the ORL-1 receptor attenuate ethanol intake in alcohol-preferring rats and suggest that the NC/ORL1 system may represent an interesting target for treatment of alcohol abuse [8].
• Intracerebroventricular (i.c.v.) injection of OFQ (1 microgram) elicited a significant decrement of pain threshold which was abolished by the repeated pretreatment with antisense oligonucleotide (ASO) to OFQ receptor [9].

High impact information on Oprl1

• In situ hybridization revealed that OFQ receptor messenger RNA was expressed in the colonic myenteric plexus but not in the smooth muscle cells, suggesting that the site of action of OFQ is neuronal [10].
• Agonist-stimulated [(35)S]GTPgammaS autoradiography also examined other G-protein-coupled receptors, including delta opioid, ORL-1, GABA(B), adenosine A(1), cannabinoid, and 5-HT(1A) [11].
• Actions of the ORL1 receptor ligand nociceptin on membrane properties of rat periaqueductal gray neurons in vitro [12].
• Moving from the orphanin FQ receptor to an opioid receptor using four point mutations [13].
• Creating a functional opioid alkaloid binding site in the orphanin FQ receptor through site-directed mutagenesis [14].

Chemical compound and disease context of Oprl1

• RATIONALE: Orphanin FQ (OFQ; also known as nociceptin), the endogenous ligand of the opioid receptor-like receptor, injected intracerebroventricularly (i.c.v.) decreases basal motor activity and basal extracellular levels of dopamine (DA) in the nucleus accumbens (Nuc Acc) in rats [15].
• Estrogen was shown to increase ORL-1 immunoreactivity in the VMH, and microinfusions of OFQ/N into the VMH facilitated lordosis behavior in a dose-dependent manner [16].
• In conclusion, N/OFQ receptor antagonist JTC-801 exerted anti-allodynic and anti-hyperalgesic effects in rats, suggesting that N/OFQ system might be involved in the modulation of neuropathic pain and inflammatory hyperalgesia [17].

Biological context of Oprl1

• The amino acid sequence of ORL1 also shares a high degree of homology with that of mu receptor [18].
• Nociceptin reversibly inhibited the DRP in a concentration-dependent manner (IC50: approximately 45 nM, maximal inhibition: approximately 50%), an effect that was antagonized by the ORL-1 receptor antagonist, J-113397 [2].
• Two C-terminal amino acids, Ser(334) and Ser(335), are required for homologous desensitization and agonist-induced phosphorylation of opioid receptor-like 1 receptors [19].
• The OFQR gene exceeds 10 kb in length and contains six exons ranging from 34 to 524 bp that are interrupted by five introns [20].
• These data suggest that unique regions in intron 1 and in the 5' flanking region of the OFQR gene contribute to the regulation of its expression in different tissues [20].

Anatomical context of Oprl1

• In general co-localization of MOR and ORL-1 receptor immunoreactivity was not observed in either perikarya or neuropil in the dorsal root ganglia, nor in the Lissauer's tract and superficial laminae of the spinal cord [21].
• We aimed at defining precisely the localization of ORL1 receptors in dorsal raphe nucleus, by means of a lesion strategy and autoradiographic studies [22].
• RNA blot hybridization and in situ hybridization analysis revealed that ROR-C mRNA is expressed in discrete regions of the rat central nervous system [23].
• Distribution of ORL-1 receptor binding and receptor-activated G-proteins in rat forebrain and their experimental localization in anterior cingulate cortex [24].
• Role of nociceptin and opioid receptor like 1 on entrainment function in the rat suprachiasmatic nucleus [6].

Associations of Oprl1 with chemical compounds

• An opioid receptor like 1 antagonist, compound B (10 microM), induced a phase delay, and this effect was blocked by nociceptin (10 microM) [6].
• Substituting Ser(334) or Ser(335) with alanine greatly impaired nociceptin-induced ORL1 desensitization [19].
• In HEK 293 cells expressing wild-type ORL1 and ORL1(CDelta21), which lacks C-terminal 21 amino acids, nociceptin inhibition of adenylate cyclase activity exhibited homologous desensitization after 1 h pretreatment of nociceptin [19].
• In the present study, we investigated the functional role played by C-terminal Ser/Thr residues in agonist-induced desensitization and phosphorylation of ORL1 [19].
• The cellular localization of ORL-1 receptors and activated G-proteins in area 24 was examined using two strategies: ibotenic acid injection into the cortex or undercut lesions to remove afferent axons, followed by autoradiography [24].

Regulatory relationships of Oprl1

• Opioid receptor-like 1 stimulation in the collecting duct induces aquaresis through vasopressin-independent aquaporin-2 downregulation [4].

Other interactions of Oprl1

• 1. Whole-cell patch clamp recordings were made from rat rostral ventromedial medulla (RVM) neurons in vitro to investigate the cellular actions of the opioid-like receptor ORL1 (NOP), ligand nociceptin/orphanin FQ and other putative prepronociceptin products [25].
• These observations indicate that MOR and ORL-1 receptors are expressed predominantly on different fiber systems in these regions [21].
• These converging antagonist and AS ODN data firmly implicate the kappa(1)-opioid receptor and the KOR-1 and KOR-3/ORL-1 opioid receptor genes in the mediation of dynorphin-induced feeding [26].
• Nociceptin, an endogenous ligand for the opioid receptor-like (ORL-1) G-protein coupled receptor, has been found to inhibit the local axon reflex-mediated neurogenic inflammation by suppressing the release of vasoactive neuropeptides from sensory afferent terminals [2].
• The DRG cell line F11 was found to express preproN/OFQ, but not ORL1, and, therefore, is well suited to study the mechanisms of N/OFQ gene regulation in vitro [3].

Analytical, diagnostic and therapeutic context of Oprl1

• Nociceptin activation of ORL1 (opioid receptor-like 1 receptor) has been shown to antagonize mu receptor-mediated analgesia at the supraspinal level [18].
• Co-immunoprecipitation experiments demonstrate that ORL1 dimerizes with muR and that intracellular C-terminal tails of ORL1 and muR are required for the formation of ORL1/muR heterodimer [18].
• [(3)H]nociceptin/orphanin FQ (N/OFQ) and N/OFQ-stimulated [(35)S]GTPgammaS autoradiography in rat brain were used to localize ORL-1 receptors and activated G-proteins, respectively [24].
• Molecular cloning of the orphanin FQ receptor gene and differential tissue expression of splice variants in rat [20].
• By using double label immunohistochemistry and confocal microscopy, the present study investigates the distribution of MOR and ORL-1 receptors in regions of the rat nervous system that are involved with nociceptive processing [21].

References