Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the role of ORL1 (opioid receptor-like 1) receptor in the bowel movement, we investigated the effect of nociceptin on colonic contraction and transit in rats. Nociceptin (0.1-100 nM) concentration-dependently caused an immediate tonic contraction followed by rhythmic waves of contractions in the isolated colon. The response to nociceptin (10 nM) was not affected by the classical opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine. Suppression of effect of inhibitory neurotransmitters using pituitary adenylate cyclase activating polypeptide(6-38) (PACAP-(6-38); 3 microM), vasoactive intestinal polypeptide(10-28) (VIP-(10-28); 3 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) did not influence the nociceptin-induced contractions. In anesthetized rats, intravenous administration of nociceptin (1 microg/kg) or morphine (1 mg/kg) caused phasic contractions in the proximal colon. Pretreatment with naloxone (300 microg/kg, i.v.) abolished the contractions induced by morphine, but not by nociceptin. The rate of large intestinal transit was dose-dependently accelerated by nociceptin (0.03-3 microg/kg, s.c.), but was retarded by morphine (1.7-5 mg/kg, s.c.). These results indicate that stimulation of ORL1 receptor accelerates the colonic contraction and transit independently from opioid receptors.
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PMID:The effect of nociceptin, an endogenous ligand for the ORL1 receptor, on rat colonic contraction and transit. 972 56

We have recently shown that endomorphin 1, an endogenous ligand for the mu-opioid receptor, and nociceptin (Orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have substantial vasodilator activity in the hindquarters vascular bed of the rat. In the present study, the role of nitric oxide, vasodilator prostaglandins, and the opening of K+ ATP channels in mediating vasodilator responses to endomorphin 1, PL017, and DAMGO was investigated in the regional vascular bed in the rat. Under constant-flow conditions, injections of the mu-selective agonists endomorphin 1, PL017 ([N-MePhe3,D-Pro4]-morphiceptin), and DAMGO, and the ORL1 receptor agonist nociceptin/ OFQ produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1, PL017, and DAMGO, and the endothelium-dependent vasodilators acetylcholine and adrenomedullin were attenuated by the nitric oxide synthase inhibitor L-NAME (50 mg/kg IV) at a time when vasodilator responses to nociceptin/OFQ were not altered. Vasodilator responses to isoproterenol and prostaglandin E1, agents known to increase cAMP levels, and the nitric oxide donor DEA/NO were not altered by the nitric oxide synthase inhibitor. Responses to endomorphin 1, PL017, DAMGO, and nociceptin/OFQ were not altered by sodium meclofenamate at a time when vasodilator responses to arachidonic acid were reduced significantly or after administration of U-37883A at a time when vasodilator responses to levcromakalim were reduced significantly. The results of these studies indicate that responses to endomorphin 1, PL017, and DAMGO are mediated in large part by the release of nitric oxide, while responses to nociceptin/OFQ are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that responses to these peptides are not mediated by the release of vasodilator prostaglandins or the opening of K+ATP channels the hindquarters vascular bed.
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PMID:Nitric oxide release mediates vasodilator responses to endomorphin 1 but not nociceptin/OFQ in the hindquarters vascular bed of the rat. 986 68

Endomorphin 1 and 2 are newly discovered endogenous ligands for the mu-opioid receptor. We recently showed that endomorphin 1 and 2 have vasodepressor activity, and in this study, responses to a novel endomorphin analog [D-Ala2]-endomorphin 2 (TAPP) were investigated in the systemic vascular bed of the rat. Intravenous injections of TAPP, endomorphin 1, and endomorphin 2 decreased systemic arterial pressure in a dose-related manner. Decreases in systemic arterial pressure in response to TAPP were similar to vasodepressor responses to endomorphin 1 and 2 and were not altered by passage of time. Decreases in systemic arterial pressure in response to TAPP, endomorphin 1, and endomorphin 2 were attenuated by the opioid receptor antagonist naloxone (2 mg/kg, i.v.) when the vasodepressor response to the ORL1-receptor agonist nociceptin (orphanin FQ) was not altered. Decreases in systemic arterial pressure in response to TAPP, endomorphin 1 and 2, and acetylcholine were attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg, i.v.) when decreases in systemic arterial pressure in response to nociceptin and calcitonin gene-related peptide (CGRP) were not altered. These results indicate that TAPP, endomorphin 1, and endomorphin 2 decrease systemic arterial pressure by a naloxone-sensitive mechanism and suggest that the vasodepressor response to TAPP, endomorphin 1 and 2, but not nociceptin, is mediated by the release of nitric oxide.
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PMID:Vasodepressor responses to [D-Ala2]-endomorphin 2 (TAPP) are mediated by an L-NAME-sensitive mechanism in the rat. 1002 37

The endomorphin peptides, endogenous ligands for the mu-opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have substantial vasodilator activity in the rat. The roles of nitric oxide, vasodilator prostaglandins, and the opening of K+ATP channels in mediating vasodilator responses to these novel agonists were investigated in the hindquarters vascular bed of the rat. Under constant-flow conditions, injections of the mu-selective agonists, endomorphin 1 and 2, PL017 ([N-MePhe3, D-Pro4]-morphiceptin), and DAMGO, and the ORL1 receptor agonist, nociceptin/OFQ, produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1, PL017, and DAMGO were attenuated by the nitric oxide synthase inhibitor L-NAME at a time when vasodilator responses to nociceptin/OFQ were not altered. Responses to endomorphin 1 and 2, PL017, DAMGO, and nociceptin/OFQ were not altered by the cyclooxygenase inhibitor sodium meclofenamate or the K+ATP channel blocker U-37883A. The results of these studies indicate that responses to endomorphin 1 and 2, PL017, and DAMGO are mediated in large part by the release of nitric oxide, while responses to nociceptin/OFQ are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that responses to these peptides are not mediated by the release of vasodilator prostaglandins or K+ATP channel opening in the hindquarters vascular bed.
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PMID:Vasodilator responses to the endomorphin peptides, but not nociceptin/OFQ, are mediated by nitric oxide release. 1067 45

1. Endomorphins 1 and 2, endogenous ligands for the mu-opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have vasodilator activity in the vascular bed of the hindquarters of the rat. In the present study, the role of nitric oxide (NO), vasodilator prostaglandins and the opening of KATP channels in mediating vasodilator responses to these novel agonists was investigated in the rat. 2. Under constant-flow conditions, injections of endomorphins 1 and 2, PL017 ([N-MePhe3,D-Pro4]-morphiceptin), nociceptin and Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1 and 2, acetylcholine and adrenomedullin, were attenuated by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at a time when vasodilator responses to nociceptin, adrenomedullin and the NO donor diethylamine/NO were not altered. 3. Vasodilator responses to endomorphins 1 and 2, nociceptin, PL017 and DAMGO were not altered after administration of sodium meclofenamate at a time when vasodilator responses to arachidonic acid were reduced significantly or after administration of U-37883A at a time when vasodilator responses to levcromakalim were reduced significantly. 4. The results of these studies indicate that vasodilator responses to endomorphins 1 and 2, PL017 and DAMGO are mediated, in large part, by the release of NO, whereas vasodilator responses to nociceptin are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that the vasodilator responses to these peptides are not due to the release of vasodilator prostaglandins or the opening of KATP channels in the hindquarters vascular bed of the rat.
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PMID:Role of nitric oxide in mediating vasodilator responses to opioid peptides in the rat. 1190 89

Prophylactic intravenous (i.v.) injections of a selective agonist of ORL1 receptors nociceptin (orphanin FQ) in a dose of 0.4 mg/kg prevented the development of aconitine-induced arrhythmia in rats narcotized with diethyl ether or chloralose. Pretreatment with L-NAME (50 mg/kg) completely abolished this effect of orphanin FQ, while the pretreatment with indomethacin (10 mg/kg) only attenuated the agonist effect, rather than abolished it completely. At the same time, pretreatment with hexamethonium (10 mg/kg) or glibenclamide (3 mg/kg) had no effect on the nociceptin-dependent cardiac tolerance to the arrhythmogenic action of aconitine. Intracerebroventricular (i.c.v.) infusion of orphanin FQ (36 microg) also prevented the onset of aconitine-induced arrhythmia, but this effect was completely abolished by hexamethonium. It is concluded that the antiarrhythmic action of nociceptin with respect to aconitine-induced arrhythmia upon i.v. and i.c.v. administration is explained by different mechanisms. In the former case, the effect of orphanin FQ is related to the activation of NO synthase and cyclooxygenase, while the central action involves the vegetative nervous system.
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PMID:[The mechanism of antiarrhythmic action of the endogenous ORL1 receptor agonist nociceptin]. 1570 12

The mas-related genes (Mrgs, also known as sensory neuron-specific receptors, SNSRs) are specifically expressed in small diameter sensory neurons in the trigeminal and dorsal root ganglia, suggesting an important role of the receptors in pain transmission. The present study aimed to investigate the underlying mechanism of the nociceptive effects after activation of MrgC, and the interaction between MrgC and N/OFQ-NOP receptor system in modulation of nociception in mice. Intrathecal (i.t.) administration of [Tyr(6)] gamma2-MSH(6-12), the most potent agonist for MrgC receptor, produced a significant hyperalgesic response as assayed by tail withdrawal test and a series of characteristic nociceptive responses, including biting, licking and scratching, in a dose-dependent manner (0.01-10 pmol and 0.01-10 nmol, respectively) in mice. These pronociceptive effects induced by [Tyr(6)] gamma2-MSH(6-12) were inhibited dose-dependently by co-injection of competitive NMDA receptor antagonist D-APV, non-competitive NMDA receptor antagonist MK-801, and nitric oxide (NO) synthase inhibitor L-NAME. However, the tachykinin NK(1) receptor antagonist L-703,606, and tachykinin NK(2) receptor antagonist MEN-10,376, had no influence on pronociceptive effects elicited by [Tyr(6)] gamma2-MSH(6-12). In other groups, [Tyr(6)] gamma2-MSH(6-12)-induced nociceptive responses were bidirectionally regulated by the co-injection of N/OFQ. N/OFQ inhibited nociceptive responses at high doses (0.01-1 nmol), but potentiated the behaviors at low doses (1 fmol-3 pmol). Furthermore, both hyperalgesia and nociceptive responses were enhanced after the co-administration with NOP receptor antagonist [Nphe(1)]N/OFQ(1-13)-NH(2). These results suggest that intrathecal [Tyr(6)] gamma2-MSH(6-12)-induced pronociceptive effects may be mediated through NMDA receptor-NO system in the spinal cord, and demonstrate the interaction between MrgC and N/OFQ-NOP receptor system in pain transmission.
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PMID:Involvement of NMDA receptor in nociceptive effects elicited by intrathecal [Tyr6] gamma2-MSH(6-12), and the interaction with nociceptin/orphanin FQ in pain modulation in mice. 1933 41