Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of leukemia inhibitory factor (LIF) on the expression of neurotransmitter synthetase and neuropeptide mRNAs in cultured rat cortical neurons were examined by reverse transcription-polymerase chain reaction. Nociceptin mRNA expression was increased by treatment with 20 or 80 ng/ml LIF for 24 h, but choline acetyl transferase, glutamic acid decarboxylase, enkephalin, dynorphin, substance P, somatostatin and galanin mRNA expression were not altered by LIF. These observations indicated a specific effect of LIF on nociceptin gene regulation in cultured cortical neurons.
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PMID:Leukemia inhibitory factor induces nociceptin mRNA in cultured rat cortical neurons. 1158 57

Nociceptin/orphanin FQ (N/OFQ), an endogenous opioid-like orphan receptor (NOP receptor, previously termed ORL1 receptor) agonist, has been found to inhibit capsaicin-induced bronchoconstriction in isolated guinea-pig lungs and in vivo. The underlying mechanisms are not clear. In the present studies, we tested the effect of N/OFQ on VR1 channel function in isolated guinea-pig nodose ganglia cells. Capsaicin increased intracellular Ca(2+) concentration in these cells through activation of vanilloid receptors. Capsaicin-induced Ca(2+) responses were attenuated by pretreatment of nodose neurons with N/OFQ (1 microM). N/OFQ inhibitory effect on the Ca(2+) response in nodose ganglia cells was antagonized by tertiapin (0.5 microM), an inhibitor of inward-rectifier K(+) channels, but not by verapamil, a voltage gated Ca(2+) channel blocker, indicating that an inward-rectifier K(+) channel is involved in N/OFQ inhibitory effect. In isolated guinea-pig bronchus, N/OFQ (1 microM) inhibited capsaicin-induced airway contraction. Tertiapin (0.5 microM) abolished the N/OFQ inhibition of capsaicin-induced bronchial contraction. Capsaicin (10 microg) increased pulmonary inflation pressure in the isolated perfused guinea-pig lungs. This response was significantly attenuated by pretreatment with N/OFQ (1 microM). Tertiapin also abolished the N/OFQ inhibitory effect on capsaicin-induced bronchoconstriction in perfused lungs. Capsaicin increased the release of substance P and neurokinin A from isolated lungs. N/OFQ (1 microM) blocked the capsaicin-induced tachykinin release. These results indicate that N/OFQ-induced hyperpolarization of tachykinin containing airway sensory nerves, through an inward-rectifier K(+) channel activation, accounts for the inhibition of capsaicin-evoked broncoconstriction.
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PMID:Nociceptin/orphanin FQ inhibits capsaicin-induced guinea-pig airway contraction through an inward-rectifier potassium channel. 1183 24

Nociceptin can induce spinal analgesia in rats. Here, we tested the ability of nociceptin to inhibit the nociceptive behavior (biting, scratching, licking) induced by intrathecal administration of N-methyl-D-aspartate (4 microg) or the tachykinin NK(1) receptor agonist, septide (0.5 microg), in rats. Intrathecal nociceptin (3-30 nmol) did not modify the NMDA-induced behavior. However, coadministration of nociceptin (1-10 nmol) inhibited the septide-induced excitatory response. This inhibition was unaffected by systemic (10 mg/kg) or intrathecal (30 nmol) administration of naloxone, but intrathecal coadministration of the ORL1 (opioid receptor-like type 1) receptor antagonist [Nphe(1)]nociceptin-(1-13)-NH(2) (30-90 nmol) prevented it, suggesting the involvement of ORL1 receptors.
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PMID:Spinal nociceptin inhibits septide but not N-methyl-D-aspartate-induced nociceptive behavior in rats. 1206 97

The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) has recently been isolated from porcine and rat brain and identified as the endogenous ligand of the N/OFQ receptor (NOP). It shows structural similarity with opioid peptides. N/OFQ has also been demonstrated in the gastrointestinal tract, where it inhibits gastrointestinal motility. The effect of N/OFQ on gastric neuroendocrine function is unknown as yet. In the isolated perfused rat stomach, N/OFQ 10(-6) M shows a small, but not significant decrease of basal somatostatin (SRIF) secretion. At the doses of 10(-12) M, 10(-10) and 10(-8) M N/OFQ has neither an effect on basal SRIF nor on basal vasoactive intestinal polypeptide (VIP), gastrin, substance P or bombesin secretion, respectively. However, gastric inhibitory polypeptide (GIP) 10(-9) M prestimulated SRIF secretion is significantly inhibited by N/OFQ 10(-8) M (-45+/-11%; p<0.05 vs. GIP). During concomitant infusion of the specific competitive NOP receptor antagonist [Nphe(1)]nociceptin(1-13)NH(2) 10(-6) M, the effect of N/OFQ is abolished (6+/-11%; p<0.05 vs. GIP and N/OFQ) while the opiate receptor antagonist naloxone 10(-6) M has no significant effect (-32+/-9%; ns vs. GIP and N/OFQ). At the higher concentration of N/OFQ 10(-6) M, the inhibition of prestimulated SRIF secretion (-58+/-6%; p<0.05 vs. GIP) is not influenced by the NOP receptor antagonist at the concentration of 10(-6) M (-49+/-9%; ns vs. GIP and N/OFQ) and 10(-5) M (-69+/-10%; ns vs. GIP and N/OFQ), respectively. On the other hand, infusion of naloxone 10(-6) M attenuates the inhibitory effect of N/OFQ 10(-6) M significantly (-21+/-6%; p<0.05 vs. GIP and N/OFQ).Thus, N/OFQ is an inhibitor of gastric somatostatin secretion. At the lower dose, this effect is transmitted via NOP receptors, while at the higher dose of 10(-6) M, the effect is at least in part mediated via opiate receptors.
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PMID:Inhibitory effect of nociceptin on somatostatin secretion of the isolated perfused rat stomach. 1213 64

Nociceptin is a peptide transmitter belonging to the opioid family. Nociceptin has recently attracted considerable interest since it appears to exhibit a number of differences to the other opioids. In the present study, we used a nociceptin antibody to map the distribution of nociceptin in the human trigeminal ganglion. In addition, we studied the nociceptin receptor at mRNA levels by RT-PCR and the vasomotor response to nociceptin in human cerebral vessels using a sensitive in vitro method. About 70% of all neuronal cells in trigeminal ganglia were nociceptin immunopositive. Nociceptin was predominantly (78%) expressed in medium-sized cells (30-60 microm). Nociceptin also distributed in small-sized cells (14% of positive cell bodies; <30 microm) and in large-sized cells (8% of positive cell bodies; >60 microm). Double immunostaining showed that in the human trigeminal ganglion nociceptin colocalized with calcitonin gene-related peptide (CGRP), substance P (SP), nitric oxide synthase (NOS) or pituitary adenylate cyclase activating peptide (PACAP). About 61% of nociceptin positive cells contained CGRP, 54% contained SP, 50% contained NOS and 68% contained PACAP. Immunoreactivity to nociceptin was not detected in human cerebral blood vessels. Reverse transcriptase-polymerase chain reaction detected the expression of nociceptin receptor mRNA in trigeminal ganglia but not in basilar arteries. To further examine whether there are functional nociceptin receptors in human cerebral arteries, a pharmacological study was done, where cerebral arteries revealed strong contractions to 60 mM K(+) and U466166 and strong relaxation to CGRP. Nociceptin failed to elicit contraction or relaxation. In conclusion, nociceptin is expressed in human trigeminal ganglia but not in cerebral blood vessels. Nociceptin is colocalized with CGRP, SP, NOS and PACAP. Nociceptin receptor mRNA is expressed in human trigeminal ganglia but not in basilar arteries. The functional role of nociceptin may be at the presynaptic level.
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PMID:Nociceptin immunoreactivity and receptor mRNA in the human trigeminal ganglion. 1257 78

Because nociceptin/orphanin FQ (N/OFQ) has both pronociceptive (hyperalgesia) and antinociceptive actions in pharmacological experiments, and there is no significant difference in the nociceptive responses between NOP(-/-) mice and their wild-type (NOP(+/+)) littermates, the physiological role of N/OFQ in pain regulation remains to be determined. Under the hypothesis that the use of molecularly distinct nociception test may reveal the pain modality-specific role of N/OFQ, we attempted to examine the physiological role of N/OFQ in pain transmission by using newly developed algogenic-induced nociceptive flexion test in NOP(-/-) and NOP(+/+) mice or NOP antagonist-treated mice. The nociceptive flexor responses upon intraplantar injection of bradykinin or substance P, which stimulates polymodal substance P-ergic fibers, were markedly potentiated in NOP(-/-) mice, compared with those in its NOP(+/+) mice. However, there were no significant changes in NOP(-/-) mice with adenosine triphosphate or prostaglandin I(2) agonist, which stimulates glutamatergic but not substance P-ergic fibers. The nocifensive responses induced by substance P (i.t.) were also potentiated in NOP(-/-) mice. On the other hand, there were no significant differences in NK1-like immunoreactivity, [(3)H]substance P binding, or NK1 gene expression in the dorsal horn of the spinal cord between NOP(-/-) and NOP(+/+) mice. In addition, NOP antagonists decreased the threshold in nociception tests driving spinal substance P neurotransmission. All these findings suggest that the N/OFQ-ergic neuron may play an in vivo inhibitory role on the second-order neurons for primary polymodal substance P-ergic fibers in the spinal cord.
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PMID:In vivo pain-inhibitory role of nociceptin/orphanin FQ in spinal cord. 1260 80

Nociceptin/orphanin FQ (N/OFQ), nocistatin, and prepro-N/OFQ 160-187 (C-peptide) are all derived from the same precursor protein. We examine the pharmacological mechanisms of nocistatin- and C-peptide-induced pronociceptive responses in a novel algogenic-induced nociceptive flexion test in mice. The intraplantar (i.pl.) injection of nocistatin- and C-peptide induced pronociceptive responses in a range of 0.01 to 10 or 1 pmol, respectively, which showed 100- to 1000-fold less potent effects than the N/OFQ. The nociceptive effects of both peptides were not affected by 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazole-2-one (J-113397) (i.pl.), an N/OFQ receptor antagonist, indicating that they are mediated by a novel mechanism independent of activation of N/OFQ receptor. Like N/OFQ, nocistatin-induced nociception was abolished by i.pl. injection of pertussis toxin, phospholipase C inhibitor, or CP-99994, a neurokinin 1 receptor antagonist, indicating that nocistatin may elicit nociception through a substance P release from nociceptor endings via activation of Gi/o and phospholipase C. The nociception was abolished by neonatal pretreatment (s.c.) with capsaicin or by i.t. pretreatment with CP-99994, but not MK-801 (i.t.), an N-methyl-d-aspartate receptor antagonist. In contrast, C-peptide-induced nociception was attenuated by the pretreatment with antisense oligodeoxynucleotide for Galphas (i.t.) and with KT-5720 (i.pl.), a cyclic AMP-dependent protein kinase inhibitor, but not with pertussis toxin. The nociception was neither attenuated by neonatal capsaicin nor by i.t. injection with CP-99994, but it was attenuated by i.t. injection with MK-801. These results suggest that nocistatin and C-peptide derived from prepro-N/OFQ stimulate distinct nociceptive fibers through different in vivo signaling mechanisms.
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PMID:Nocistatin and prepro-nociceptin/orphanin FQ 160-187 cause nociception through activation of Gi/o in capsaicin-sensitive and of Gs in capsaicin-insensitive nociceptors, respectively. 1266 41

Recent evidence suggests a role of prepronociceptin/orphanin FQ (preproN/OFQ) derived neuropeptides in nociceptive signaling. Here, we examined the expression of preproN/OFQ and the nociceptin receptor ORL1 (opioid receptor like receptor 1) in the dorsal root ganglion (DRG) of the rat in relation to that of substance P (SP) and calcitonin gene-related peptide (CGRP). Double labeling in situ hybridization revealed a constitutive expression of preproN/OFQ in a distinct minor subpopulation of very small DRG neurons with no evidence for coexpression with either SP or CGRP. However, a major subpopulation of the preproN/OFQ-positive neurons showed direct juxtaposition to SP and CGRP containing neurons. ORL1 was abundantly expressed with a high degree of coexpression with SP (72%) and CGRP (82%) suggesting that N/OFQ may presynaptically modulate primary sensory nociceptive signaling. 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.
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PMID: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. 1293 25

1. Gastro-oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Our previous results suggest that microvascular leakage induced, in the guinea-pig airways, by intra-oesophageal hydrochloric acid (HCl) infusion was mainly dependent on the release of tachykinins. Nociceptin, an endogenous ligand of the opioid receptor NOP, has been shown to inhibit bronchoconstriction and cough in guinea-pig or cat by inhibiting tachykinin release. 2. The purpose of this study was to investigate the effects of nociceptin on the intra-oesophageal HCl-induced airway microvascular leakage evaluated by Evans blue dye extravasation measurement in anaesthetised guinea-pigs pretreated with propranolol, atropine and phosphoramidon. 3. Infusion of intra-oesophageal HCl led to a significant increase in plasma extravasation in the main bronchi and trachea. This increase was abolished when animals underwent a bilateral vagotomy. 4. Airway microvascular leakage was inhibited by nociceptin (3-30 microg x kg(-1) i.v.) in a dose-dependent manner (maximal inhibition at the dose of 30 microg x kg(-1): 19.76+/-1.13 vs 90.92+/-14.00 ng x mg(-1) tissue for nociceptin and HCl infusion, respectively, in the main bronchi, P<0.01). The NOP receptor agonist [Arg(14),Lys(15)]N/OFQ mimicked the inhibitory effect of nociceptin, but at a 10-fold lower dose (3 microg x kg(-1) i.v). The NOP receptor antagonist J-113397 had no effect on plasma protein extravasation by itself, but was able to block the inhibitory effect of nociceptin. 5. Morphine (1 mg x kg(-1)) had a similar inhibitory effect as that of nociceptin. Naloxone pretreatment abolished the effect of morphine, but was enable to block the inhibitory effect of nociceptin. 6. Under similar conditions, nociceptin, in the previous range of concentration, was unable to counteract the airway microvascular leakage induced by substance P (SP). 7. These results suggest that airway plasma extravasation induced by intra-oesophageal HCl instillation might be inhibited by specific stimulation of the NOP receptor with nociceptin. Nociceptin is likely to act at a pre-junctional level, by inhibiting tachykinin release, since it was unable to prevent SP-induced airway plasma extravasation.
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PMID:Nociceptin inhibits airway microvascular leakage induced by HCl intra-oesophageal instillation. 1499 1

Chronic exposure to beta(2)-adrenoceptor agonists, especially fenoterol, has been shown to increase smooth muscle contraction to endothelin-1 in human bronchi partly through tachykinin-mediated pathways. The purpose of this work was to further investigate the role of sensory nerves in fenoterol-induced sensitization of human airways and the effect of nociceptin, a nociceptin/orphanin FQ (NOP) receptor agonist, on the increase in contraction after fenoterol exposure. Human bronchi from 62 patients were sensitized to endothelin-1 by prolonged incubation with fenoterol (0.1 microM, 15 h). The sensitizing effect of fenoterol was inhibited by high concentration of capsaicin (10 microM, 30 min before fenoterol sensitization), which induces depletion of mediators from sensory nerves, or co-incubation of fenoterol and capsazepine (1 microM), a vanilloid TRPV-1 receptor antagonist. Moreover, short pretreatment of bronchi with capsaicin (10 microM) or capsazepine (1 microM) after sensitization by fenoterol decreased the rise in smooth muscle contraction to endothelin-1. Nociceptin (1 microM) also inhibited the increased contraction in fenoterol-sensitized bronchi. Tertiapin (10 microM), an inhibitor of the inward-rectifier K(+) channels, but not naloxone (0.1 microM), a DOP/KOP/MOP receptor antagonist, prevented the inhibitory effect of nociceptin. In conclusion, fenoterol induces sensitization of human isolated bronchi to endothelin-1 in part through the stimulation of the vanilloid TRPV-1 receptor on tachykininergic sensory nerves. Nociceptin inhibits airway hyperresponsiveness via NOP receptor activation. This effect involves inward-rectifier K(+) channels.
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PMID:Nociceptin inhibits vanilloid TRPV-1-mediated neurosensitization induced by fenoterol in human isolated bronchi. 1535 28


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