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 role of neurokinin 1 (NK(1)) receptor and possible interaction between NK(1) and N-methyl-D-aspartic acid (NMDA) glutamatergic receptors were investigated on spinal c-fos expression after lower urinary tract irritation with acetic acid infusion in rats. At both levels of the first (L(1)) and sixth lumbar (L(6)) spinal cord, where most of hypogastric nerve and pelvic nerve afferent terminals project, respectively, the selective NK(1) receptor antagonist CP-99,994 dose dependently reduced the total number of c-fos protein (Fos)-positive cells. However, CP-100,263, the enantiomer of CP-99,994 with a very low affinity for NK(1) receptor, did not have any effect on the total number of Fos-positive cells. Coadministration of a low dose (1 mg/kg) of CP-99,994 and NMDA receptor antagonist (MK-801), either of which alone did not affect c-fos expression, significantly inhibited c-fos expression at both levels of the spinal cord. Regarding regional differences, the number of Fos-positive cells decreased significantly at all regions of the L(6) level, but only at the dorsal horn of the L(1) level. These results indicate that NK(1) receptor is involved in spinal c-fos expression after lower urinary tract irritation and that NK(1) and NMDA receptors have a synergistic interaction in the spinal processing of nociceptive input from the lower urinary tract.
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PMID:NK(1) receptor and its interaction with NMDA receptor in spinal c-fos expression after lower urinary tract irritation. 1218 90

Neurokinin-1 (NK(1)) receptors activated by substance P (SP) are involved in the processing of nociceptive information and are a potential target for therapy of visceral pain. We have evaluated the role of NK(1) receptors using a selective antagonist of NK(1) receptors in two animal models of colorectal hypersensitivity. The behavioral response to colorectal distension was assessed in freely moving guinea pigs by recording visceromotor reflex contractions of the abdominal musculature. Colonic hypersensitivity was induced by intracolonic administration of a chemical irritant (0.6% of acetic acid), or by acute partial restraint stress. Sensitization was characterized by an exaggerated visceromotor response to a low level of colorectal distension (10 mm Hg). In both models of colonic hypersensitivity, oral administration of TAK-637 (0.1-10 mg/kg) normalized visceromotor responses. The intracerebroventricular (10 microg/kg) or intrathecal (10 microg/kg) administration of TAK-637 inhibited colonic hypersensitivity, suggesting an interaction with central NK(1) receptors. In contrast, TAK-637 had no effect on visceromotor responses to colorectal distension at 40 mm Hg in guinea pigs with normosensitive (nonsensitized) colons. In conclusion, central NK(1) receptors play a significant role in colonic hypersensitivity induced by visceral afferent nerve sensitization from gastrointestinal origin or acute psychosomatic stress, but not in the perception of colorectal distension in animals with normosensitive colons.
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PMID:NK1 receptor-mediated mechanisms regulate colonic hypersensitivity in the guinea pig. 1266 16

Antinociceptive profiles of decursinol were examined in ICR mice. Decursinol administered orally (from 5 to 200 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured by the tail-flick and hot-plate tests. In addition, decursinol attenuated dose-dependently the writhing numbers in the acetic acid-induced writhing test. Moreover, the cumulative response time of nociceptive behaviors induced by an intraplantar formalin injection was reduced by decursinol treatment during the both 1st and 2nd phases in a dose-dependent manner. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of TNF-alpha (100 pg), IL-1 beta (100 pg), IFN-gamma (100 pg), substance P (0.7 microg) or glutamate (20 microg) was dose-dependently diminished by decursinol. Intraperitoneal (i.p.) pretreatment with yohimbine, methysergide, cyproheptadine, ranitidine, or 3,7-dimethyl-1-propargylxanthine (DMPX) attenuated inhibition of the tail-flick response induced by decursinol. However, naloxone, thioperamide, or 1,3-dipropyl-8-(2-amino-4-chloro-phenyl)-xanthine (PACPX) did not affect inhibition of the tail-flick response induced by decursinol. Our results suggests that decursinol shows an antinociceptive property in various pain models. Furthermore, antinociception of decursinol may be mediated by noradrenergic, serotonergic, adenosine A(2), histamine H(1) and H(2) receptors.
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PMID:Antinociceptive mechanisms of orally administered decursinol in the mouse. 1275 41

To characterize the antinociceptive profiles of Angelica gigas NAKAI (ANG; Korean angelica), methanol extract from the dried roots of ANG was made and mice were administered orally at the various doses (from 0.25 to 3 g/kg). ANG produced the increased latencies of the tail-flick and hot-plate paw-licking responses in a dose-dependent manner. In acetic acid-induced writhing test, ANG dose-dependently decreased writhing numbers. Moreover, the cumulative response time of nociceptive behaviors induced by intraplantar formalin injection was reduced during both the 1st and the 2nd phases in a dose-dependent manner in ANG-treated mice. Furthermore, oral administration of ANG did not cause licking, scratching and biting responses induced by TNF-alpha (100 pg), IFN-gamma (100 pg) or IL-1beta (100 pg) injected intrathecally (i.t.), especially at higher dose (3 g/kg). Additionally, in ANG treated mice, the cumulative nociceptive response time for i.t. administration of substance P or capsaicin was dose-dependently diminished. Finally, nociceptive responses elicited by i.t. injection of glutamate (20 microg), N-methyl-D-aspartic acid (60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (13 ng) or kainic acid (12 ng) were decreased by oral administration of ANG. Our results suggest that ANG produces antinociception via acting on the central nervous system and shows antinociceptive profiles in various pain models, especially inflammatory pain.
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PMID:Antinociceptive profiles of crude extract from roots of Angelica gigas NAKAI in various pain models. 1295 72

Chromogranin A (CgA) is an acidic protein identified within a large variety of endocrine cells. Colocalized with catecholamines in chromaffin cells, CgA is a prohormone precursor of small biologically active peptides. Vasostatin (CgA 1-76) is the most conserved fragment of CgA and chromogranin A 47-66 peptide (CgA 47-66) possesses potent antimicrobial activities. The aim of this study was to test the hypothesis that CgA 47-66 may be involved in mechanisms modulating nociception. Thus, we used acetic acid (AA) which produces a delayed inflammatory response and episodes of abdominal writhing, a marker of pain, when injected intraperitoneally (i.p.) to rats. Administration (i.p.) of CgA 47-66 induced specific opposite dose-dependent effects depending on concentration. That is, CgA 47-66 below 0.5 mg/kg produced antinociceptive effects, whereas at 2 mg/kg it produced a marked pronociceptive effect. The latter effect was blocked by diltiazem and indomethacin. CgA 47-66-induced antinociceptive effects on AA-induced responses were reversed when the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF 9-41 was i.p. injected to animals prior to AA and CgA 47-66 administration. The administration of i.p. calcitonin gene-related peptide (CGRP) or substance P (SP) evoked dose-dependent abdominal writhing; this effect was abolished when CgA 47-66 was injected. The present data suggest, for the first time, that a fragment of CgA, CgA 47-66, possesses potent antinociceptive effects at low doses. Although the mechanism triggered by this peptide is unknown, CRF receptors are likely to be involved.
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PMID:Effects of a chromogranin-derived peptide (CgA 47-66) in the writhing nociceptive response induced by acetic acid in rats. 1512 Apr 81

The nociceptive effects of i.p administration of a synthetic peptide (CgA4-16) derived from chromogranin A (CgA) were studied on a model of inflammatory (somato-visceral) pain. Inflammatory mediators participate in controlling the activity of enterochromaffin cells that store and release chromogranins. Adult male Wistar rats were injected i.p with diluted acetic acid (AA) to induce abdominal writhes. Pharmacological agents were injected prior to CgA4-16 and/or AA together. While i.p CgA4-16 alone did not produce any effect, the peptide increased the number of abdominal constrictions induced by i.p AA administration in a dose-related manner. To determine the possible mechanisms involved in CgA4-16 produced pronociceptive effect, i.p diltiazem or indomethacin were tested. The pronociceptive effect induced by CgA4-16 was blocked by pretreatment of either substance. I.p administration of CGRP, substance P (SP) or capsaicin evoked dose-related abdominal writhing. CgA4-16, 20 min prior to CGRP or capsaicin, potentiated the nociceptive effects induced by CGRP or capsaicin, but not those induced by SP. Taken together, these data suggest for the first time that a CgA-derived peptide may modulate inflammatory pain.
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PMID:The effect of a chromogranin A-derived peptide (CgA4-16) in the writhing nociceptive response induced by acetic acid in rats. 1530 24

Mu-, kappa- and delta-opioid receptor agonists are reported to attenuate the acetic-acid-induced abdominal constriction response in mice. NK-1, -2 and -3 receptor antagonists also display activity in several visceral pain models. As the gerbil NK-1 receptor is comparable to the human receptor, we evaluated the efficacy of NK-1, -2 and -3 receptor antagonists and opioids (both alone and in combination) in the writhing test in this species. The effects of a selective L-type calcium (Ca2+) channel antagonist on the writhing response were also assessed to determine the contribution of Ca2+ channel antagonism to the antinociceptive effects of the NK-1 antagonists. Gerbils received subcutaneous injections of either the mu-opioids morphine or fentanyl, the kappa-opioid U50,488-H, the delta-opioid SNC80, NK-1 antagonists R116301, CP-96,345 or GR203040, the NK-2 antagonist SR-48968, the NK-3 antagonist SR-142801 or the Ca2+ channel antagonist nimodipine. Writhing was evoked 1 h after treatment by intraperitoneal injection of 0.2 ml 1% acetic acid solution and the frequency was recorded. Morphine, fentanyl and U50,488-H attenuated the writhing response dose dependently with complete inhibition occurring at the highest doses. SNC80 did not significantly attenuate the writhing response even at a dose of 40 mg/kg. The tachykinin NK-1 antagonists CP-96,345 and GR203040, the NK-2 antagonist SR-48968 and the NK-3 antagonist SR-142801 reduced the writhing frequency although without complete inhibition. The NK-1 antagonist R116301 displayed limited activity at doses up to 40 mg/kg. Nimodipine did not exhibit any antinociceptive efficacy in this assay. Adding the NK-1, -2 or -3 antagonists to the opioids did not improve the efficacy of the opioids. Selective NK antagonists may therefore be effective in a visceral nociception assay in gerbils but do not modulate opioid action.
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PMID:Attenuation of the gerbil writhing response by mu-, kappa- and delta-opioids, and NK-1, -2 and -3 receptor antagonists. 1538 92

The mixture of the two pentacyclic triterpenes alpha-amyrin and beta-amyrin, isolated from the resin of Protium kleinii and given by intraperitoneal (i.p.) or oral (p.o.) routes, caused dose-related and significant antinociception against the visceral pain in mice produced by i.p. injection of acetic acid. Moreover, i.p., p.o., intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of alpha,beta-amyrin inhibited both neurogenic and inflammatory phases of the overt nociception caused by intraplantar (i.pl.) injection of formalin. Likewise, alpha,beta-amyrin given by i.p., p.o., i.t., or i.c.v. routes inhibits the neurogenic nociception induced by capsaicin. Moreover, i.p. treatment with alpha,beta-amyrin was able to reduce the nociception produced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesia caused by glutamate. On the other hand, in contrast to morphine, alpha,beta-amyrin failed to cause analgesia in thermal models of pain. The antinociception caused by the mixture of compounds seems to involve mechanisms independent of opioid, alpha-adrenergic, serotoninergic, and nitrergic system mediation, since it was not affected by naloxone, prazosin, yohimbine, DL-p-chlorophenylalanine methyl ester, or L-arginine. Interestingly, the i.p. administration of alpha,beta-amyrin reduced the mechanical hyperalgesia produced by i.pl. injection of carrageenan, capsaicin, bradykinin, substance P, prostaglandin E2, 8-Br-cAMP, and TPA in rats. However, the mixture of compounds failed to alter the binding sites of [3H]bradykinin, [3H]resiniferatoxin, or [3H]glutamate in vitro. It is concluded that the mixture of triterpene alpha-amyrin and beta-amyrin produced consistent peripheral, spinal, and supraspinal antinociception in rodents, especially when assessed in inflammatory models of pain. The mechanisms involved in their action are not completely understood but seem to involve the inhibition of protein kinase A- and protein kinase C-sensitive pathways.
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PMID:Antinociceptive properties of mixture of alpha-amyrin and beta-amyrin triterpenes: evidence for participation of protein kinase C and protein kinase A pathways. 1562 26

The antinociceptive effect of nicotine administered intracereboventricularly (i.c.v.) or intrathecally (i.t) in several pain models was examined in the present study. We found that i.t. treatment with nicotine (from 5 to 20 g) dose-dependently blocked pain behavior revealed during the second phase, but not during the first phase in the formalin test. In addition, i.c.v. treatment with nicotine (from 0.1 to 10 microg) dose-dependently attenuated pain behavior revealed during both the first and second phases. In addition to the formalin test, nicotine administered i.c.v. or i.t. attenuated acetic acid-induced writhing response. Furthermore, i.c.v. or i.t. administration of nicotine did not cause licking, scratching and biting responses induced by substance P, glutamate, TNF-alpha (100 pg), IL-1beta (100 pg) and INF-gamma (100 pg) injectied i.t. The antinociception induced by supraspinally-administered nicotine appears to be more effective than that resulting from spinally administered nicotine. Our results suggest that nicotine administration induces antinociception by acting on the central nervous system and has differing antinociceptive profiles according to the various pain models.
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PMID:Antinociceptive effect of nicotine in various pain models in the mouse. 1578 53

We studied the anatomical properties of parasympathetic postganglionic neurons in the frog tongue and their modulatory effects on taste cell responses. Most of the parasympathetic ganglion cell bodies in the tongue were found in extremely small nerve bundles running near the fungiform papillae, which originate from the lingual branches of the glossopharyngeal (GP) nerve. The density of parasympathetic postganglionic neurons in the tongue was 8000-11,000/mm(3) of the extremely small nerve bundle. The mean major axis of parasympathetic ganglion cell bodies was 21 microm, and the mean length of parasympathetic postganglionic neurons was 1.45 mm. Electrical stimulation at 30 Hz of either the GP nerve or the papillary nerve produced slow hyperpolarizing potentials (HPs) in taste cells. After nicotinic acetyl choline receptors on the parasympathetic ganglion cells in the tongue had been blocked by intravenous (i.v.) injection of D-tubocurarine (1 mg/kg), stimulation of the GP nerve did not induce any slow HPs in taste cells but that of the papillary nerve did. A further i.v. injection of a substance P NK-1 antagonist, L-703,606, blocked the slow HPs induced by the papillary nerve stimulation. This suggests that the parasympathetic postganglionic efferent fibers innervate taste cells and are related to a generation of the slow HPs and that substance P is released from the parasympathetic postganglionic axon terminals. When the resting membrane potential of a taste cell was hyperpolarized by a prolonged slow HP, the gustatory receptor potentials for NaCl and sugar stimuli were enhanced in amplitude, but those for quinine-HCl and acetic acid stimuli remained unchanged. It is concluded that frog taste cell responses are modulated by activities of parasympathetic postganglionic efferent fibers innervating these cells.
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PMID:Taste cell responses in the frog are modulated by parasympathetic efferent nerve fibers. 1624 66


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