Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Neuronal plasticity associated with altered sensations arising from tissue damage involves both established (e.g. substance P and excitatory amino acids) and novel (e.g. nitric oxide and metabolites of arachidonic acid) mediators released from terminals of primary afferent neurons or synthesised in the spinal cord. These and other mediators lead to activity-dependent synaptic plasticity and enhanced sensitivity to noxious stimuli (hyperalgesia). Activation of the N-methyl-D-aspartate (NMDA) receptor results in a calcium-dependent production of nitric oxide, while activation of alpha-amino-3-hydroxy-5-methylisoxazole-5-propionate (AMPA)-and 1,3- trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD)-sensitive glutamate receptors results in a phospholipase A2 (PLA2)-mediated production of different intracellular mediators, including arachidonic acid. Thermal hyperalgesia requires NMDA receptor activation and is primarily mediated by production of nitric oxide. Mechanical hyperalgesia requires AMPA and metabotropic glutamate receptor coactivation, and is primarily mediated by cyclo-oxygenase products of arachidonic acid metabolism.
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PMID:Spinal mediators of hyperalgesia. 752 81

In chronically cannulated rats, microinjection of a competitive metabotropic glutamate receptor (mGluR) antagonist, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), into the dorsal striatum at doses of 0.4, 2 and 10 micrograms/1 microliter did not affect basal levels of preprodynorphin, substance P and preproenkephalin mRNAs in the dorsal striatum as revealed by quantitative in situ hybridization. However, intrastriatal MCPG (0.08, 0.4 and 2 micrograms/1 microliter) dose-dependently attenuated increases in the three mRNA expression induced by acute amphetamine injection (2 mg/kg, i.p.). MCPG had no significant effect on spontaneous, and amphetamine-stimulated, behavioral activities. These data indicate that activation of MCPG-sensitive mGluRs is necessary for upregulation of striatal neuropeptide mRNA expression in response to amphetamine exposure. However, the mGluR activity is not implicated in maintaining basal levels of the peptide gene expression in the striatum.
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PMID:Intrastriatal injection of the metabotropic glutamate receptor antagonist MCPG attenuates acute amphetamine-stimulated neuropeptide mRNA expression in rat striatum. 893 69

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

It was examined electron microscopically in the rat if a metabotropic glutamate receptor, mGluR7, might be localized in axon terminals of nociceptive, primary afferent fibers in laminae I and II of the spinal dorsal horn. Nociceptive nature of axon terminals showing mGluR7-like immunoreactivity (mGluR7-LI) was indicated by binding to the isolectin I-B4 from Griffonia simplicifolia (I-B4), or by substance P-like immunoreactivity (SP-LI). Axon terminals labeled with immunogold particles indicating mGluR7-LI were usually filled with round synaptic vesicles and were in asymmetric synaptic contact with dendritic or somatic profiles; occasionally they contained pleomorphic vesicles and were in symmetric synaptic contact with somatic profiles in lamina II. The double-labeling studies revealed that most of axon terminals with I-B4 labeling as well as a small population of axon terminals with SP-LI, showed mGluR7-LI. About one-third or much smaller population of axon terminals with mGluR7-LI in laminae I and II were labeled, respectively, with I-B4 or SP-LI; these were in asymmetric synaptic contact with dendritic profiles.
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PMID:Localization of a metabotropic glutamate receptor, mGluR7, in axon terminals of presumed nociceptive, primary afferent fibers in the superficial layers of the spinal dorsal horn: an electron microscope study in the rat. 908 Apr 55

Metabotropic glutamate receptors (mGluRs) can be divided into three groups based on sequence homology and pharmacology. We studied expression of group I mGluRs (mGluR1 and mGluR5) in identified neurons of the rat neostriatum, neocortex, and hippocampus using in situ hybridization. Tissue sections were hybridized with radiolabeled RNA probes for mGluR1 or mGluR5 and digoxygenin labeled RNA probes detecting somatostatin (SOM), preproenkephalin (ENK), preprotachykinin (SP), glutamic acid decarboxylase 67 (GAD67), parvalbumin (PARV), or choline acetyltransferase (ChAT) mRNA. In the striatum, mGluR1 hybridization signal was observed in all six neuronal populations. The strongest signal was found in SP-positive neurons, with a lower signal in ENK-positive neurons. All striatal interneurons were labeled less intensely than ENK- and SP-positive projection neurons. For striatal mGluR5 mRNA, both SP- and ENK-positive projection neurons were intensely labeled, but only GAD67-positive interneurons exhibited a significant signal. In the neocortex and hippocampus, mGluR1 and mGluR5 hybridization signals were studied in SOM-, GAD67-, and PARV-positive neurons. Hybridization signal for mGluR1 mRNA was intense in SOM-positive neurons of the cortex, CA1, CA3, and dentate gyrus, and weaker in GAD67-positive neurons of CA3 and dentate gyrus. MGluR5 signals were intensely labeled in SOM-, GAD67- and PARV-positive neuronal populations of the cortex and hippocampus. SOM-positive neurons were more intensely labeled in the hippocampus than cortex.
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PMID:Expression of group one metabotropic glutamate receptor subunit mRNAs in neurochemically identified neurons in the rat neostriatum, neocortex, and hippocampus. 933 23

The effects of substance P and related tachykinins on intrinsic membrane properties and synaptic responses of neurons in cortical slices were determined. Substance P had no detectable effect on membrane properties of principal neurons in layer II or V of the rat medial entorhinal cortex or on neurons in either layer of the anterior cingulate cortex. Specific agonists at the neurokinin1-receptor were also without effect as were agonists at both neurokinin1- and neurokinin3-receptors. Substance P hyperpolarized a small number of principal neurons. These responses were weak and desensitized with repeated applications. Similar effects were seen with other neurokinin1-receptor agonists. Excitatory synaptic potentials mediated by either alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate- or N-methyl-D-aspartate-receptors in principal neurons of the entorhinal cortex were unaffected by substance P. Responses of entorhinal neurons to iontophoretically applied glutamate and N-methyl-D-aspartate were also unaffected. Inhibitory synaptic potentials mediated by either GABA(A)- or GABA(B)-receptors in entorhinal neurons were slightly but consistently enhanced by substance P. Neurons identified as interneurons on the basis of their firing characteristics were consistently depolarized by substance P. These responses also desensitized with repeated applications. Spontaneous epileptiform discharges evoked in entorhinal cortex by perfusion with a GABA(A)-receptor antagonist (bicuculline), were reduced in frequency and, sometimes, in duration by substance P. This effect was mimicked by other neurokinin1-receptor agonists and blocked by neurokinin1-receptor antagonists. It was also mimicked by neurokinin A but not by a specific neurokinin1-receptor agonist. The reduction in frequency of discharges was also mimicked by a GABA(B)-receptor agonist, L-baclofen, and blocked by the GABA(B)-receptor antagonist, CGP55845A. Neurokinin B, and a specific neurokinin1-receptor agonist (senktide), increased the frequency and (sometimes) duration of epileptiform discharges. Substance P could also increase frequency but this usually succeeded or preceded a decrease in frequency. The effect of neurokinin B was reduced by a metabotropic glutamate receptor antagonist. Substance P appears to have little direct effect on principal neurons of the entorhinal cortex but may hyperpolarize them indirectly by activating interneurons and releasing GABA. This indirect inhibition may be responsible for the ability of substance P to reduce the frequency of epileptiform discharges in the entorhinal cortex and may suggest that neurokinin1-receptor agonists have potential as anticonvulsant drugs.
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PMID:Tachykinins may modify spontaneous epileptiform activity in the rat entorhinal cortex in vitro by activating GABAergic inhibition. 950 45

A detailed description of the localization of neurons containing various neuropeptides in the supramammillary complex (SUM) is provided. Further, the neurochemical character of supramammillohippocampal and supramammilloseptal projecting neurons was investigated. The following experiments were performed: (a) immunocytochemistry for each of the eight different neuropeptides investigated, in animals pretreated or not with colchicine, and perfused in fixative containing or lacking acrolein; (b) a thorough mapping study of the localization of immunolabelled neurons at three rostrocaudal levels; (c) double-tracing retrograde labelling for two-directional neuronal projections combined with immunocytochemistry, to study neurochemical character of the projecting neurons. The observations are: (1) each type of immunolabelled elements, such as calretinin, calbindin, VIP, substance P, CCK and metabotropic glutamate receptor 1a immunopositive neurons has a characteristic localization; (2) no parvalbumin- and enkephalin-containing neurons are present in the SUM; and (3) a small population of calretinin-containing and a small number of calretinin-negative supramammillohippocampal neurons located in the lateral area also project to the medial septum-diagonal band region of the septal complex.
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PMID:Topographic localization of calretinin, calbindin, VIP, substance P, CCK and metabotropic glutamate receptor immunoreactive neurons in the supramammillary and related areas of the rat. 950 82

Substance P and glutamate are present in primary afferent C-fibers and play important roles in persistent inflammatory and neuropathic pain. In the present study, we have examined whether activation of different glutamate receptor subtypes modulates the release of substance P evoked by the C-fiber selective stimulant capsaicin (1 microM) from rat trigeminal nucleus slices. The selective NMDA glutamate receptor agonist L-CCG-IV (1-10 microM) enhanced capsaicin-evoked substance P release about 100%. This facilitatory effect was blocked by 0.3 microM MK-801, a selective NMDA receptor antagonist. The metabotropic glutamate receptor agonists L-AP4 (group III) and DHPG (group I) (30-100 microM) inhibited capsaicin-evoked substance P release by approximately 60%. These inhibitory effects were blocked by the selective metabotropic glutamate receptor antagonist (+/-)-MCPG (5 microM). On the other hand, AMPA and kainate (0.1-10 microM), did not significantly affect capsaicin-evoked substance P release. Thus, substance P release from non-myelinated primary afferents, and possibly nociception, may be under the functional antagonistic control of some metabotropic and ionotropic glutamate receptor subtypes.
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PMID:Opposite modulation of capsaicin-evoked substance P release by glutamate receptors. 1052 15

Effects of glutamate on synaptic transmission in the submucosal plexus of guinea-pig small intestine were studied with intracellular electrophysiological recording methods. Glutamate suppressed stimulus-evoked slow excitatory postsynaptic potentials (EPSPs) and increased the amplitude of slow inhibitory postsynaptic potentials (IPSPs) in submucosal neurons. The actions of glutamate were mimicked by the group I metabotropic glutamate receptor (mGluRs) agonist DHPG, but not by the group II agonist S-4C3HPG, the group III agonist L-AP4, or selective agonists for ionotropic glutamate receptors (iGluRs). Glutamate actions were suppressed by the selective group I mGluRs antagonist S-4CPG, but not by group II and III mGluRs antagonist CPPG or iGluRs antagonists. Glutamate suppressed substance P- and 5-HT-evoked slow EPSP-like responses and potentiated norepinephrine-induced slow IPSP-like responses. The results suggest that group I mGluRs mediate glutamate-induced suppression of slow EPSPs and potentiation of slow IPSPs in S-type uniaxonal submucosal neurons.
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PMID:Glutamate modulates neurotransmission in the submucosal plexus of guinea-pig small intestine. 1054 20

Inhibition of "leak" potassium (K+) channels is a widespread CNS mechanism by which transmitters induce slow excitation. We show that TASK-1, a two pore domain K+ channel, provides a prominent leak K+ current and target for neurotransmitter modulation in hypoglossal motoneurons (HMs). TASK-1 mRNA is present at high levels in motoneurons, including HMs, which express a K+ current with pH- and voltage-dependent properties virtually identical to those of the cloned channel. This pH-sensitive K+ channel was fully inhibited by serotonin, norepinephrine, substance P, thyrotropin-releasing hormone, and 3,5-dihydroxyphenylglycine, a group I metabotropic glutamate receptor agonist. The neurotransmitter effect was entirely reconstituted in HEK 293 cells coexpressing TASK-1 and the TRH-R1 receptor. Given its expression patterns and the widespread prevalence of this neuromodulatory mechanism, TASK-1 also likely supports this action in other CNS neurons.
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PMID:TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. 1071 94


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