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)

1. Modulation of plateau properties in dorsal horn neurones was studied in a transverse slice preparation of the spinal cord of the turtle. In plateau-generating neurones high frequency stimulation of the ipsilateral dorsal root (10-20 Hz, 0.5-2 min) produced a slow depolarization (2.9 +/- 0.6 mV, mean +/- S.E.M.; n = 6) and enhanced the properties mediated by dihydropyridine-sensitive Ca2+ channels. The tetanic stimulus facilitated wind-up and after-discharges even when fast synaptic transmission was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-20 microM), (+/-)-2-amino-5-phosphonopentanoic acid (AP5, 100 microM), bicuculline (10-20 microM) and strychnine (5-20 microM). 2. Application of cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 10-50 microM) produced a slow depolarization (5.9 +/- 0.5 mV, n = 21) accompanied by an increase in input resistance (28.8 +/- 5.1%, n = 12). 3. ACPD increased the excitability by facilitating the plateau properties. In the presence of tetrodotoxin (TTX, 1 microM) a lower threshold and a slower decay of the plateau potential were observed. These effects resulted in facilitation of wind-up and prolonged after-discharges. 4. All ACPD-induced effects were blocked by alpha-methyl-4-carboxyphenylglycine (MCPG, 0.5-1 mM), a selective antagonist of metabotropic glutamate receptors. The selective agonist for the type I metabotropic glutamate receptor ((RS)-3,5-dihydrophenylglycine (DHPG, 50 microM)) reproduced all the effects of ACPD. 5. Application of a supposed neuromodulator, substance P (1-2 microM) produced a transient depolarization (4 +/- 0.6 mV) lasting 4-6 min during continued application of substance P. Variable effects on the input resistance were observed, a slight increase (12 +/- 2%) being the most frequent. In 61% of the cells, substance P induced a clear increase in excitability with no detectable change in input resistance or membrane potential. 6. The effects of substance P on plateau properties were indistinguishable from those produced by ACPD. Unlike the transient depolarization, the facilitation of the plateau properties persisted in the presence of the agonist. 7. The substance P-induced facilitation of the plateau potential was blocked by GR 82334 (5-10 microM), a selective NK-1 tachykinin-receptor antagonist, and was not affected by MEN 10376 (2 microM), a selective NK-2 antagonist. 8. The facilitation of plateau properties produced by dorsal root stimulation was also reduced by antagonists of metabotropic glutamate receptors and NK-1 tachykinin receptors. 9. We propose that modulation of postsynaptic plateau properties in dorsal horn neurones by activation of type I metabotropic glutamate receptors and NK-1 tachykinin receptors is involved in processing nociceptive information.
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PMID:Modulation of plateau properties in dorsal horn neurones in a slice preparation of the turtle spinal cord. 908 Mar 74

Drimanial, a new sesquiterpene isolated from the barks of the plant Drimys winteri (Winteraceae), given systemically, intraplantarly, or by spinal or supraspinal routes, produced pronounced antinociception against both phases of formalin-induced licking. The systemic injection of drimanial also inhibited, in a graded manner, the pain-related behaviours induced by intraplantar or intrathecal (i.t.) administration of glutamate. Moreover, drimanial also caused marked inhibition of the nociception induced by i.t. administration of a metabotropic glutamate agonist (1S,3R)-ACPD, without affecting nociceptive responses induced by ionotropic agonists (NMDA, kainate, AMPA) or by substance P. The antinociception caused by drimanial was not influenced by naloxone, nor did it interfere with the motor coordination of animals in the rota-rod test. Furthermore, drimanial caused graded inhibition of [(3)H]glutamate binding in cerebral cortical membranes from mice, with an IC(50) value of 4.39 micro M. Together, these results provide strong evidence indicating that the sesquiterpene drimanial produces antinociception in mice at peripheral, spinal and supraspinal sites. An interaction with metabotropic glutamate receptors seems to contribute to the mechanisms underlying its antinociceptive action.
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PMID:Evidence for the involvement of glutamatergic receptors in the antinociception caused in mice by the sesquiterpene drimanial. 1224 63

This study aimed to investigate further the mechanisms involved in the antinociception caused by dipyrone, given by intraperitoneal (i.p.) or intrathecal (i.t.) routes. The intraperitoneal administration of dipyrone to mice 30 min prior resulted in a significant and dose-related inhibition of the biting responses induced by i.t. injection of glutamate, trans-ACPD or substance P (SP). In addition, dipyrone given by i.t. route, 15 min before glutamate, trans-ACPD or SP, also produced a significant reduction in their nociceptive effects. In addition, dipyrone given by i.t. route, 15 min before glutamate, trans-ACPD or SP, also produced a significant reduction in their nociceptive effects. Dipyrone, given either systemically (i.p.) or by i.t. route also caused a dose-dependent inhibition of phorbol myristate acetate (PMA)-induced nociception. Given by systemic route, dipyrone inhibited PMA-induced paw oedema formation. Collectively, these results extend previous data from our group indicating that glutamatergic-mediated pain responses, specifically those mediated by metabotropic receptor subtype, together with inhibition of neurokinin NK(1)-mediated response, account for the antinociceptive action of dipyrone in mice. Furthermore, we have also produced experimental evidence indicating that the activation of the protein kinase C-dependent pathway plays a role in the dipyrone antinociceptive action.
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PMID:Evidence for the involvement of metabotropic glutamatergic, neurokinin 1 receptor pathways and protein kinase C in the antinociceptive effect of dipyrone in mice. 1501 64

This study examined the role of glutamatergic system in the ascorbic acid (AA)-induced antinociception in chemical behavioural models of nociception in mice. AA (0.3-10 mg/kg, i.p.) produced significant inhibition of both phases of formalin-induced licking, with mean ID50 values of 4.0 and 3.2 mg/kg and inhibitions of 56+/-4 and 60+/-7% for the early and second phase of the nociception caused by formalin, respectively. AA (1-5 mg/kg, i.p.) also produced significant inhibition of glutamate-induced nociception with mean ID50 value of 2.1 mg/kg and inhibition of 66+/-5%. Furthermore, AA (3 mg/kg, i.p.) caused marked inhibition of nociceptive response induced by intrathecal injection of glutamate, NMDA, AMPA, kainate and substance P, with inhibitions of 49+/-9, 42+/-7, 34+/-8, 38+/-5 and 65+/-8%, respectively. In contrast, AA at the same dose did not affect the biting response induced by the metabotropic agonist trans-ACPD. Taken together, present results indicate that AA, at low systemic doses, produces a rapid onset and consistent antinociception in mice when assessed in several models of chemical nociception, an action that is likely mediated by an interaction with ionotropic, but not metabotropic, glutamate receptors.
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PMID:Evidence for the involvement of glutamatergic system in the antinociceptive effect of ascorbic acid. 1588 14

The present study was designed to investigate further the mechanisms involved in the antinociception caused by diphenyl diselenide in behavioral model of pain in mice. Diphenyl diselenide (1-100 mg/kg), given orally, produced significant inhibition of the biting behavior induced by intrathecal (i.t.) injection of glutamate (175 nmol/site) and N-methyl-d-aspartate (NMDA; 450 pmol/site), with mean ID(50) values of 45.92 (39.74-60.4) and 55.77 (36.52-77.5) mg/kg respectively. However, diphenyl diselenide completely failed to affect the nociception induced by alpha-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA; 135 pmol/site), (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 50 nmol/site) and kainate (110 pmol/site). This compound also reduced the nociceptive response induced by substance P (SP) (135 ng/site, i.t.), interleukin 1beta (IL-1beta; 1 pg/site), tumor necrosis factor-alpha (TNF-alpha; 0.1 pg/site), bradykinin (BK; 0.1 microg/site) and capsaicin (30 ng/site) with mean ID(50) values of 16.22, 7.06, 6.06, 4.18 and 7.90 mg/kg, respectively. Together, these results indicate that diphenyl diselenide produced antinociception at spinal sites, with a possible interaction with glutamatergic pathways, more specifically via interaction with NMDA receptors, peptidergic or vanilloid systems.
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PMID:Spinal mechanisms of antinociceptive action caused by diphenyl diselenide. 1761 8

Humirianthera ampla Miers is a member of the Icacinaceae family and presents great amounts of di and triterpenoids. These chemical constituents in roots of Humirianthera ampla sustain not only the ethnopharmacological use against snake venom, but also some anti-inflammatory and analgesic properties of the plant. In this study we investigated the antinociceptive action of the ethanolic extract (EE) from roots of the Humirianthera ampla in chemical and thermal models of pain in mice. The oral treatment with ethanolic extract dose-dependently inhibited glutamate-, capsaicin- and formalin-induced licking. However, it did not prevent the nociception caused by radiant heat on the tail-flick test. The ethanolic extract (30 mg/kg) caused marked inhibition of the nociceptive biting response induced by glutamate, (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), N-methyl-d-aspartate (NMDA) and substance P. The antinociception caused by ethanolic extract was significantly attenuated by naloxone, l-arginine, WAY100635, ondansetron or ketanserin, but not by caffeine or naloxone methiodide. In conclusion, the ethanolic extract from roots of Humirianthera ampla produces antinociception against neurogenic and inflammatory models of nociception. The mechanisms of antinociception involve nitric oxide, opioid, serotonin and glutamate pathways. Therefore, our results support the ethnopharmacological use of the Humirianthera ampla against inflammatory and painful process caused by snake venom.
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PMID:Antinociceptive action of ethanolic extract obtained from roots of Humirianthera ampla Miers. 1790 Aug 39

Metabotropic glutamate receptors (mGluRs) are expressed abundantly in the spinal cord and have been shown to play important roles in the modulation of nociceptive transmission and plasticity. In this study, the involvement of metabotropic glutamate receptor 5 (mGluRs) in the nociceptive response induced by intrathecal injection (i.t.) of excitatory aminoacids, substance P (SP), bradykinin (BK) and cytokines in mice was demonstrated. The administration of 2-methyl-6-(phenylethynyl)-pyridine (MPEP; 10-50 nmol/site, i.t.) caused a significant inhibition in the nociceptive response induced by glutamate and trans-ACPD with maximal inhibitory effects of 36 +/- 7% and 56 +/- 5%, respectively. MPEP completely failed to affect the nociception induced by alpha-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA; 135 pmol/site), kainate (110 pmol/site) and N-methyl-D-aspartate (NMDA; 450 pmol/site). MPEP also reduced the nociceptive response induced by SP (135 ng/site, i.t.), BK (0.1 microg/site), tumor necrosis factor-alpha (TNF-alpha; 0.1 pg/site) and interleukin-1beta (IL-1beta; 1 pg/site) with maximal inhibitions of 29 +/- 5%, 37 +/- 5%, 83 +/- 3% and 88 +/- 1%, respectively. Together, these results indicate the involvement of mGluRs, more specifically of subtype-5, in the nociceptive response induced by i.t. injection of excitatory aminoacids, SP, BK and cytokines in mice.
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PMID:Effect of a metabotropic glutamate receptor 5 antagonist, MPEP, on the nociceptive response induced by intrathecal injection of excitatory aminoacids, substance P, bradykinin or cytokines in mice. 1855 52

The present study was designed to investigate further the mechanisms involved in the antinociception caused by bis-selenide in behavioral model of pain in mice. Bis-selenide (5-50 mg/kg), given orally, produced significant inhibition of the antinociceptive behavior induced by intrathecal (i.t.) injection of glutamate (175 nmol/site), kainate (110 pmol/site) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 50 nmol/site) and the maximal inhibitions observed were 57+/-5, 46+/-7 and 73+/-3%, respectively. Bis-selenide failed to affect the nociception induced by alpha-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA; 135 pmol/site) and N-methyl-d-aspartate (NMDA; 450 pmol/site). This compound also reduced the nociceptive response induced by tumor necrosis factor-alpha (TNF-alpha; 0.1 pg/site), interleukin-1beta (IL-1beta; 1 pg/site), substance P (SP) (135 ng/site, i.t.) and capsaicin (30 ng/site) and the inhibitions observed were 81+/-3%, 88+/-1%, 77+/-3 and 67+/-3, respectively. The oral administration of bis-selenide (25-50 mg/kg) in mice caused a significant increase in the reaction time to thermal stimuli in the hot plate test and the mean ID(50) value (and the 95% confidence limits) was 20.37 (15.00-25.74) mg/kg. The antinociceptive effect caused by bis-selenide (50 mg/kg, p.o.) on the hot plate test in mice was reversed by intrathecal (i.t.) injection of some K(+) channel blockers such as tetraethylammonium (TEA, non-selective voltage-dependent K(+) channel inhibitor) and glibenclamide (ATP-sensitive K(+) channel inhibitor), but not apamin and charybdotoxin (large- and small-conductance Ca(2+)-activated K(+) channel inhibitors, respectively). Together, these results indicate that bis-selenide produces antinociception at spinal sites through the activation of ATP-sensitive and voltage-gated K(+) channels and interaction with kainate and trans-ACDP receptors as well as vanilloid and neuropeptide receptors and pro-inflammatory cytokines.
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PMID:Spinal mechanisms of antinociceptive effect caused by oral administration of bis-selenide in mice. 1868 Jul 35

It is well known that adenine-based purines exert multiple effects on pain transmission. Recently, we have demonstrated that intracerebroventricular (i.c.v.) administered guanine-based purines are antinociceptive against chemical and thermal pain models in mice. The present study was designed to further investigate the antinociceptive effects of guanosine in mice. Animals received an intrathecal (i.t.) injection of vehicle (0.1 mN NaOH) or guanosine (10 to 400 nmol). Measurements of cerebrospinal fluid (CSF) purine levels and spinal cord glutamate uptake were performed. Guanosine produced dose-dependent antinociceptive effects against tail-flick, hot-plate, intraplantar (i.pl.) capsaicin, and i.pl. glutamate tests. Additionally, i.t. guanosine produced significant inhibition of the biting behavior induced by i.t. injection of glutamate (175 nmol/site), AMPA (135 pmol/site), kainate (110 pmol/site), trans-ACPD (50 nmol/site), and substance P (135 ng/site), with mean ID(50) values of 140 (103-190), 136 (100-185), 162 (133-196), 266 (153-461) and 28 (3-292) nmol, respectively. However, guanosine failed to affect the nociception induced by NMDA (450 pmol/site) and capsaicin (30 ng/site). Intrathecal administration of guanosine (200 nmol) induced an approximately 120-fold increase on CSF guanosine levels. Guanosine prevented the increase on spinal cord glutamate uptake induced by i.pl. capsaicin. This study provides new evidence on the mechanism of action of guanosine presenting antinociceptive effects at spinal sites. This effect seems to be at least partially associated with modulation of glutamatergic pathways by guanosine.
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PMID:Spinal mechanisms of antinociceptive action caused by guanosine in mice. 1937 22

The present study investigated the possible involvement of the glutamatergic and neurokinin systems in the antinociception caused by triterpene 3beta, 6beta, 16beta-trihydroxylup-20(29)-ene (TTHL) in mice. TTHL given by intraperitoneal (i.p., 2.1-65.5micromol/kg), intraplantar (i.pl., 6.5-65.5nmol/paw) or intrathecal (i.t., 21.8-655nmol/site) routes, produced dose-dependent inhibition of glutamate-induced nociception with ID(50) values of 12micromol/kg; 34.2nmol/paw; 233.8nmol/site and inhibitions of 78+/-6; 82+/-4 and 77+/-8%, respectively. I.t. injection of TTHL (6.5-218nmol/site, co-administered) also caused significant and dose-dependent reduction of nociceptive response induced by i.t. injection of glutamate (175nmol/site), with ID(50) value of 54.5nmol/site and inhibition of 51+/-6%. Moreover, TTHL (65.5nmol/site) co-injected by i.t. route with agonist caused marked reduction of nociceptive responses induced by N-methyl-d-aspartate (NMDA, 450pmol/site), (+/-)-1-aminocyclopentane-trans-1,3 dicarboxylic acid (trans-ACPD, 10nmol/site) and substance P (100pmol/site), with inhibitions of 81+/-7; 79+/-7; 81+/-11%, respectively. Conversely, TTHL had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 135pmol/site) and kainic acid (kainate, 110pmol/site)-induced nociception. Moreover, the association of sub-effective doses of TTHL (6.5nmol/site, i.t.) and MK-801(1nmol/site, i.t.; non-competitive NMDA antagonist) or (RS)-MCPG (30nmol/site, i.t.; non-selective group I/group II metabotropic glutamate receptor antagonist) produced a synergic antinociceptive effect in the nociception induced by NMDA or trans-ACPD, respectively. Together, these results provide experimental evidence for the involvement of the glutamatergic system (NMDA and metabotropic glutamate receptors) in the antinociceptive action caused by TTHL in mice.
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PMID:Spinal antinociception evoked by the triterpene 3beta, 6beta, 16beta-trihydroxylup-20(29)-ene in mice: evidence for the involvement of the glutamatergic system via NMDA and metabotropic glutamate receptors. 1976 85


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