Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q13519 (OFQ)
 1,265 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine whether nociceptin/orphanin FQ (NC), the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor, is able to block hypophagia induced by either stress or central administration of corticotropin releasing factor (CRF) in rats. A marked reduction in food consumption was observed following exposure to 15 min intermittent electric footshock, 60 min physical immobilization or after intracerebroventricular (i.c.v.) injection of CRF (0.1-1.0 microgram/rat). i.c.v. pretreatment with NC (0.1-2.0 micrograms/rat) completely abolished the hypophagic effect induced by stress or by i.c.v. CRF injection. The same i.c.v. doses of NC did not modify food consumption in food deprived rats and did not modify the anorexic effect induced by lipopolysaccharide, suggesting that the effect of NC is selective for anorexia induced by stress or CRF. These findings provide original evidence that NC attenuates stress-induced anorexia, presumably by acting as a functional CRF antagonist.
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PMID:Nociceptin/orphanin FQ inhibits stress- and CRF-induced anorexia in rats. 1133 81

There are now four types of opioid receptors. The new designations OP(1), OP(2) and OP(3) correspond, respectively, to the classic delta-, kappa- and micro-nomenclature. OP(4) was previously known as ORL(1), the receptor for the endogenous heptadecapeptide nociceptin/orphanin FQ. Although the cellular effects of nociceptin resemble those of conventional OP(1), OP(2), and OP(3) opioid agonists, its effects on nociceptive processes are quite different. Nociceptin produces spinal analgesia but appears to antagonize the effects of opioids. Following the recent synthesis of the nonpeptide OP(4) agonist Ro-64-6198 by Hoffmann-La Roche and the nonpeptide OP(4) antagonist J-113397 by Banyu, the nociceptin-OP(4) system now represents a viable and intriguing new target for drug design. OP(4) agonists may be of use in the management of neuropathic pain, anxiety, anorexia, epilepsy, drug dependence, male impotence, hypertension, cerebral ischemia and neurogenic bladder. They may also serve as novel diuretics and to help to reduce gastrointestinal motility. OP(4) antagonists may be of use as general analgesics and in the improvement of memory function. This review covers the recent exciting progress in this field, compares the actions of OP(4) agonists and antagonists with those of classic opioids, and seeks to predict some of the untoward effects that may be seen with such drugs.
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PMID:The nociceptin receptor as a potential target in drug design. 1281 96

Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid N/OFQ receptor (NOP), possesses marked functional anti-stress and anti-corticotropin-releasing factor (CRF) actions. We have shown that intracerebroventricular injection of N/OFQ reverses the hypophagic effect induced by stress or by CRF given intracerebroventricularly. To shed new light on the mechanisms involved in the anti-CRF action of N/OFQ, we investigated the ability of N/OFQ to prevent CRF-induced anorexia after microinjection studies into brain areas of potential interest in the control of feeding behavior and coexpressing NOP and CRF receptors. These areas include the bed nucleus of the stria terminalis (BNST), the central amygdala (CeA), the locus ceruleus (LC), the ventromedial hypothalamus (VMH), the paraventricular nucleus (PVN), and the dorsal raphe (DR). The results demonstrated that the anorectic effect of 0.04 nmol of CRF per rat (200 ng per rat) given intracerebroventricularly is reversed by pretreatment with 0.01-0.21 nmol of N/OFQ per rat (25-500 ng per rat) injected into the BNST but not into the CeA, LC, VMH, PVN, or DR. Microinjection of 0.01-0.02 nmol of CRF per site (50-100 ng per site) into the BNST but not into the CeA or the LC induced marked anorexia in food-deprived rats. Pretreatment with 0.01-0.21 nmol of N/OFQ per site (25-500 ng per site) into the BNST also blocked the anorectic action of 0.02 nmol of CRF per site (100 ng per site) given in the same area. Finally, intra-BNST microinjection of 0.01-0.21 nmol of N/OFQ per site (25-500 ng per site) did not modify food intake in either food-sated or food-deprived rats. These data demonstrate that the BNST is involved in the modulation of CRF-induced anorexia, which is prevented by activation of N/OFQ receptors.
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PMID:The bed nucleus is a neuroanatomical substrate for the anorectic effect of corticotropin-releasing factor and for its reversal by nociceptin/orphanin FQ. 1456 74

Almost 10 years after the discovery of Orphanin FQ / Nociceptin (OFQ/N) a large number of synthetic small molecule agonists and antagonists have been developed and tested in various physiological assays. Together with the academic work on the physiological functions of OFQ/N, we now have compelling evidence that this neuropeptide system might represent a valuable target for the development of drugs treating a variety of psychiatric disorders. Most prominently, the anti-stress and anxiolytic effects of OFQ/N agonists have been investigated although clinical trials have not yet been launched. Other possible applications of OFQ/N agonists and antagonists include treatment of depression, anorexia and rewarding aspects of drug addiction. This paper will summarize current developments and highlight the scientific achievements that have been made to elucidate the functions of OFQ/N with respect to psychiatric disorders.
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PMID:The Orphanin FQ / Nociceptin receptor as a novel drug target in psychiatric disorders. 1661 Oct 94

Central injection of Nociceptin/Orphanin FQ (N/OFQ), inhibits the anorectic effect of corticotropin-relasing factor (CRF) and stress in rats. Recently, Urocortin II (Ucn II) and Urocortin III (Ucn III), two selective CRF(2) receptor agonists, have been identified. Here, we investigated the effect of intracerebroventricular (ICV) injection of 0.25, 0.75, 1.50 or 3 nmol/rat of Ucn II or Ucn III on food and water intake in food deprived rats. The effect of N/OFQ on Ucn II and UCNIII-induced anorexia was also studied. Results showed a greater inhibition of food consumption by Ucn II than Ucn III. Pretreatment with N/OFQ (0.25-2.0 nmol/rat) did not block the effects of Ucn II and UCNIII. Conversely, injection of N/OFQ (0.25-2.0 nmol/rat) blocked the anorectic effect of CRF (0.1 nmol/rat). These findings suggest that N/OFQ selectively prevent the anorectic effect mediated by activation of the CRF(1) receptor system.
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PMID:Activation of the nociceptin/orphanin FQ system is unable to reverse CRF2 receptor mediated anorexia in the rat. 1705 37

The advance of functional genomics revealed the superfamily of G-protein coupled receptors (GPCRs). Hundreds of GPCRs have been cloned but many of them are orphan GPCRs with unidentified ligands. The first identified orphan GPCR is the opioid receptor like orphan receptor, ORL1. It was cloned in 1994 during the identification of opioid receptor subtypes and was de-orphanized in 1995 by the discovery of its endogenous ligand, nociceptin or orphanin FQ (N/OFQ). This receptor was renamed as N/OFQ peptide (NOP) receptor. Several selective ligands acting at NOP receptors or other anti-N/OFQ agents have been reported. These include N/OFQ-derived peptides acting as agonists (cyclo[Cys(10),Cys(14)]N/OFQ, [Arg(14), Lys(15)]N/OFQ, [pX]Phe(4)N/OFQ(1-13)-NH(2), UFP-102, [(pF)Phe(4),Aib(7), Aib(11),Arg(14),Lys(15)]N/OFQ-NH(2)) or antagonists (Phe(1)psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)-NH(2), [Nphe(1)]N/OFQ(1-13)-NH(2), UFP-101, [Nphe(1), (pF)Phe(4),Aib(7),Aib(11),Arg(14),Lys(15)]N/OFQ-NH(2)), hexapeptides, other peptide derivatives (peptide III-BTD, ZP-120, OS-461, OS-462, OS-500), non-peptide agonists (NNC 63-0532, Ro 64-6198, (+)-5a compound, W-212393, 3-(4-piperidinyl)indoles, 3-(4-piperidinyl) pyrrolo[2,3-b]pyridines) and antagonists (TRK-820, J-113397, JTC-801, octahydrobenzimidazol-2-ones, 2-(1,2,4-oxadiazol-5-yl)-1 H-indole, N-benzyl-D-prolines, SB-612111), biostable RNA Spiegelmers specific against N/OFQ, and a functional antagonist, nocistatin. Buprenorphine and naloxone benzoylhydrazone are two opioid receptor ligands showing high affinity for NOP receptors. NOP receptor agonists might be beneficial in the treatment of pain, anxiety, stress-induced anorexia, cough, neurogenic bladder, edema, drug dependence, and, less promising, in cerebral ischemia and epilepsy, while antagonists might be of help in the management of pain, depression, dementia and Parkinsonism. N/OFQ is also involved in cardiovascular, gastrointestinal and immune regulation. Altered plasma levels of N/OFQ have been reported in patients with various pain states, depression and liver diseases. This review summarizes the pharmacological characteristics of, and studies with, the available NOP receptor ligands and their possible clinical implications.
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PMID:Nociceptin/orphanin FQ peptide receptors: pharmacology and clinical implications. 1726 36

The NOP receptor (formerly referred to as opiate receptor-like 1, ORL-1, LC132, OP(4), or NOP(1)) is a G protein-coupled receptor that shares high homology to the classic opioid MOP, DOP, and KOP (mu, delta, and kappa, respectively) receptors and was first cloned in 1994 by several groups. The NOP receptor remained an orphan receptor until 1995, when the endogenous neuropeptide agonist, known as nociceptin or orphanin FQ (N/OFQ) was isolated. Five years later, a group at Hoffmann-La Roche reported on the selective, nonpeptide NOP agonist Ro 64-6198, which became the most extensively published nonpeptide NOP agonist and a valuable pharmacological tool in determining the potential of the NOP receptor as a therapeutic target. Ro 64-6198 is systemically active and achieves high brain penetration. It has subnanomolar affinity for the NOP receptor and is at least 100 times more selective for the NOP receptor over the classic opioid receptors. Ro 64-6198 ranges from partial to full agonist, depending on the assay. Preclinical data indicate that Ro 64-6198 may have broad clinical uses, such as in treating stress and anxiety, addiction, neuropathic pain, cough, and anorexia. This review summarizes the pharmacology and preclinical data of Ro 64-6198.
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PMID:The pharmacology of Ro 64-6198, a systemically active, nonpeptide NOP receptor (opiate receptor-like 1, ORL-1) agonist with diverse preclinical therapeutic activity. 1746 93