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)

1. Effects of the alpha 2-adrenoceptor agonists, UK14304 and clonidine, the 5-HT1 receptor agonist, sumatriptan and the kappa-opioid receptor agonist, GR103545, on sensory neurotransmission in histamine-contracted guinea-pig isolated pulmonary artery (GPPA) have been studied. 2. Electrical field stimulation (EFS) induced frequency-dependent relaxations of histamine-contracted GPPA, which were attenuated by tetrodotoxin and capsaicin pretreatment but not by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). 3. Substance P (0.3 microM) induced relaxations which were subject to rapid tachyphylaxis. Neither the NK1 receptor antagonist, (+/-)-CP 96,345, nor desensitization to substance P had any effect of EFS-induced relaxations of histamine-contracted GPPA. 4. Calcitonin gene-related peptide (CGRP; 3 and 30 nM) induced concentration-dependent relaxations of histamine-contracted GPPA. The putative CGRP receptor antagonist, CGRP8-37 (1 microM), markedly attenuated EFS-induced relaxations as well as relaxations induced by a low concentration of CGRP. 5. Sumatriptan (0.1 and 1 microM) and the selective kappa-opioid receptor agonist, GR103545 (10 and 100 nM) had no effect on EFS-induced relaxations of histamine-contracted GPPA. In contrast, the alpha 2-adrenoceptor agonists UK14304 (1-100 nM) and clonidine (300 nM) attenuated responses to EFS, the attenuation of UK14304 (100 nM) being reversed by yohimbine (300 nM). 6. It is concluded that in GPPA, where a presynaptic inhibition of sensory neurotransmission by alpha 2-adrenoceptor activation could be shown, there was no evidence for such modulation by either sumatriptan-sensitive 5-HT1 receptors or kappa-opioid receptors.
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PMID:Sensory nerve-mediated relaxation of guinea-pig isolated pulmonary artery: prejunctional modulation by alpha 2-adrenoceptor agonists but not sumatriptan. 768 95

1. Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown. 2. Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by assessing the efficacy of agents that inhibit specific components of spinal nociceptive processing. 3. Dose-dependent inhibition of tactile allodynia in diabetic rats was noted with the N-type calcium channel antagonist SNX 239, the alpha2-adrenoceptor agonist dexmedetomidine, the mu-opioid receptor agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 and the non-NMDA receptor antagonist NBQX. 4. No effect on tactile allodynia was noted after intrathecal administration of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the cyclo-oxygenase inhibitor ketorolac, the L-type calcium channel inhibitor diltiazem or any vehicle. 5. These data suggest that the tactile allodynia of diabetic rats involves spinal glutamatergic pathways but is not associated with spinal release of nitric oxide or prostaglandins.
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PMID:Spinal pharmacology of tactile allodynia in diabetic rats. 942 Dec 98

Endomorphin 1 and 2, newly discovered endogenous ligands for the mu-opioid receptor, have vasodepressor activity in the rat. In the present study, the mechanism mediating hemodynamic responses to endomorphin 2 and the endomorphin analog [D-Ala2]endomorphin 2 (TAPP) was investigated in the rat. Intravenous injections of TAPP and endomorphin 2 produced similar dose-dependent decreases in systemic arterial pressure and were approximately 10-fold more potent than Met-enkephalin. TAPP and endomorphin 2 decreased heart rate, cardiac output, and total peripheral resistance. Under constant-flow conditions, injections of TAPP and endomorphin 2 into the perfusion circuit produced decreases in hindquarter perfusion pressure, and vasodilator responses were attenuated by the opioid receptor antagonist naloxone. Hindquarter vasodilator responses to TAPP and endomorphin 2 were attenuated by the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg iv), whereas responses to the endothelium-independent vasodilators calcitonin gene-related peptide, diethylamine/nitric oxide, and isoproterenol were not changed. Hindquarter vasodilator responses to TAPP and endomorphin 2 were not altered by the cyclooxygenase inhibitor sodium meclofenamate, the ATP-dependent K+ channel antagonist U-37883A, or the presence of a time-delay coil in the perfusion circuit. These results indicate that vasodilator responses to TAPP and endomorphin 2 are mediated by the activation of a naloxone-sensitive opioid receptor and the release of nitric oxide from the endothelium within the hindquarter vascular bed of the rat.
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PMID:D-[Ala2]endomorphin 2 and endomorphin 2 have nitric oxide-dependent vasodilator activity in rats. 961 81

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

Endotoxin (lipopolysaccharide, LPS) and interleukin-1 (IL-1) administration induce hypophagia in rodents. Both IL-1 and LPS are known to activate cerebral norepinephrine and serotonin metabolism, and IL-1 affects that of acetylcholine and histamine. Each of these neurotransmitters has been implicated in feeding behavior. Therefore, the ability of specific antagonists of the above neurotransmitter systems to counteract feeding responses to peripherally injected mIL-1beta and LPS was studied. Feeding was assessed in nondeprived mice by measuring the intake of sweetened milk in a 30-min period, as well as daily food pellet intake. LPS and mIL-1beta reliably reduced milk intake, and often reduced food pellet intake and body weight. Treatment of the mice with peripherally administered alpha-adrenergic (phentolamine or prazosin) or 3-adrenergic antagonists (propranolol), either alone or in combination, did not significantly alter the hypophagic responses to mIL-1beta or LPS. Mice in which cerebral norepinephrine was depleted with DSP-4 or 6-hydroxydopamine also displayed the usual hypophagia in response to mIL-1beta and LPS. The hypophagic responses to mIL-1beta and LPS were not affected by the histaminergic antagonists, pyrilamine (H1), cimetidine (H2), thioperamide (H3), or the histamine-depleting agent, alpha-fluoromethylhistidine, nor by the muscarinic cholinergic antagonist, scopolamine. The responses to mIL-l1 were also unaffected by the dopamine receptor antagonist, haloperidol, the opioid receptor antagonist, naloxone, and the NO synthase inhibitor, L-NAME. These results suggest that adrenergic, dopaminergic, histaminergic, cholinergic, opioid or nitric oxide systems are not essential for the hypophagia induced by IL-1, and that multiple redundant pathways may be involved in illness-related hypophagia.
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PMID:Endotoxin- and interleukin-1-induced hypophagia are not affected by adrenergic, dopaminergic, histaminergic, or muscarinic antagonists. 1046 92

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

Controversies surround the possible long-term physiological and psychological consequences of opioid use. Analgesic tolerance and addiction are commonly at the center of these controversies, but other concerns exist as well. A growing body of evidence suggests that hyperalgesia caused by the chronic administration of opioids can occur in laboratory animals and in humans. In these studies we describe a murine model of opioid-induced hyperalgesia (OIH). After the treatment of mice for 6 days with implanted morphine pellets followed by their removal, both thermal hyperalgesia and mechanical allodynia were documented. Additional experiments demonstrated that prior morphine treatment also increased formalin-induced licking behavior. These effects were intensified by intermittent abstinence accomplished through administration of naloxone during morphine treatment. Experiments designed to determine if the mu-opioid receptor mediated OLH in our model revealed that the relatively-selective mu-opioid receptor agonist fentanyl induced the thermal hyperalgesia and mechanical allodynia characteristic of OIH when administered in intermittent boluses over 6 days. In complimentary experiments we found that CXBK mice which have reduced mu-opioid receptor binding displayed no significant OIH after morphine treatment. Finally, we explored the pharmacological sensitivities of OIH. We found that the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the heme oxygenase (HO) inhibitor tin protoporphyrin (Sn-P) dose-dependently reduced OIH in this model while the NSAID indomethacin had no effect. Thus we have characterized a murine model of OIH which will be useful in the pursuit of the molecular mechanisms underlying this phenomenon.
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PMID:A murine model of opioid-induced hyperalgesia. 1116 71

In this study, we attempted to identify the mechanisms of paeoniflorin on antinociceptive effects in mice. Paeoniflorin (48, 96, 240, 480 microg, i.c.v.) showed dose-related antinociception both on the early and late phases of formalin test in mice. Moreover, paeoniflorin (48 microg, i.c.v.) could potentiate the antinociception of morphrine (0.5, 1.0 mg/kg, s.c.) in the formalin test. However, the antinociceptive effects of paeoniflorin were not potentiated by L-arginine (600 mg/kg, i.p.) or antagonized by beta-funaltrexamine (beta-FNA) (10 microg, i.c.v.), ICI-174,864 (1 microg, i.c.v.) and ryanodine (10 ng, i.c.v.) on both the early and late phases of formalin test. L-NAME (75 mg/kg, i.p.) could reverse the effect of paeoniflorin on the late phase of formalin test. Naloxone (1 mg/kg, i.p.) and nor-binaltorphimine (nor-BNI) (1 microg, i.c.v.) could block the paeoniflorin-induced antinociception on the early phase of formalin test. These results suggested that the central antinociceptive effects of paeoniflorin on formalin test in mice were mediated by the activation of kappa-opioid receptor and not related to the increase of intracellular calcium.
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PMID:Effects of paeoniflorin on the formalin-induced nociceptive behaviour in mice. 1129 61


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