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)

Substance P produces analgesia when administered to mice in very small doses by the intraventricular route (1.25 to 5 nanograms per mouse). The analgesic effect can be blocked by naloxone. At higher doses (greater than 50 nanograms per mouse), this activity is lost. At these higher doses, however, substance P produced hyperalgesia when combined with naloxone and analgesia when combined with baclofen [beta-(4-chlorophenyl)-gamma-aminobutyric acid]. Substance P may have dual actions in brain, releasing endorphins at very low doses and directly exciting neuronal activity in nociceptive pathways at higher doses.
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PMID:Dual actions of substance P on nociception: possible role of endogenous opioids. 20 12

Administration of i.t. calcium has been shown to produce effects which are opposite to those observed when calcium is injected into the brain. The purpose of this study was to elucidate the mechanism of the antinociceptive action of calcium (i.t.). Injection of calcium (i.t.) produced antinociceptive effects in the tail-flick and p-phenylquinone (PPQ) stretching tests. The ED50 value for calcium (i.t.) in the PPQ test was 4.8 (4.2-5.5) nmol per mouse vs. 344 (251-469) nmol per mouse for calcium (i.t.) in the tail-flick test. The antinociceptive effects of calcium (i.t.) were attenuated significantly in the tail-flick test by pretreatment with naloxone (i.t.) (AD50 value = 200 pmol/mouse) and ICI-174,864 (i.t.) (AD50 value = 20 nmol/mouse), but not by the kappa receptor-selective antagonist nor-BNI. The antinociceptive effects of calcium (i.t.) were attenuated significantly in the PPQ test by pretreatment with naloxone (i.t.) (AD50 value = 50 pmol/mouse) and norbinaltorphimine (i.t.) (AD50 value = 110 pmol/mouse), but not by the delta receptor-selective antagonists naltrindole and ICI-174, 864. Administration of calcium (i.t.) significantly enhanced the antinociceptive effects of mu [D-Ala2,N-Me-Phe4,Gly-ol]enkephalin, delta [D-Pen2,D-Pen5]enkephalin and kappa (U50,488H) opioid receptor-selective peptides. The injection of the dibutyryl derivative of cyclic AMP (i.t.), as well as forskolin (i.t.), blocked the antinociceptive effects of calcium (i.t.) (AD50 values = 39 nmol and 1.7 nmol/mouse, respectively). Injection of apamin (AD50 value = 2.9 pmol/mouse) and charybodotoxin (58 fmol/mouse), blockers of calcium-gated potassium channels, significantly blocked calcium (i.t.). The antinociceptive effects of calcium (i.t.) were also blocked by verapamil (30 and 60 nmol/mouse), theophylline (275 nmol/mouse) and substance P (7.4 nmol/mouse, i.t.). Thus, the data indicate that the mechanism underlying the antinociceptive effect of calcium (i.t.) involves mediation, at least in part, by opioid peptides, alterations in intraneuronal cyclic AMP and/or neuronal hyperpolarization, and decreased release of substance P. The administration of calcium (i.t.) may also enhance the release of adenosine as a significant factor in the antinociceptive effects of the calcium.
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PMID:A proposed mechanism of action for the antinociceptive effect of intrathecally administered calcium in the mouse. 134 58

The effects of intrathecal administration of prostaglandins on pain responses in conscious mice were evaluated by using hot plate and acetic acid writhing tests. Prostaglandin D2 (0.5-3 ng/mouse) had a hyperalgesic action on the response to a hot plate during a 3-60 min period after injection. Prostaglandin E2 showed a hyperalgesic effect at doses of 1 pg to 10 ng/mouse, but the effect lasted shorter (3-30 min) than that of prostaglandin D2. Similar results were obtained by acetic acid writhing tests. The hyperalgesic effect of prostaglandin D2 was blocked by simultaneous injection of a substance P antagonist (greater than or equal to 100 ng) but not by AH6809, a prostanoid EP1-receptor antagonist. Conversely, prostaglandin E2-induced hyperalgesia was blocked by AH6809 (greater than or equal to 500 ng) but not by the substance P antagonist. Prostaglandin F2 alpha had little effect on pain responses. These results demonstrate that both prostaglandin D2 and prostaglandin E2 exert hyperalgesia in the spinal cord, but in different ways.
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PMID:Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2 alpha to conscious mice. 232 44

Peptide-containing nerve fibers were found to be numerous in the glandular stomach of the rat and mouse. The immunoreactive neuropeptides demonstrated included vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastrin-releasing peptide (GRP), substance P (SP), enkephalin, somatostatin, cholecystokinin, and neuropeptide Y (NPY). The density and distribution of the various peptide-containing fibers did not differ overtly between the pyloric and oxyntic gland areas except for the GRP fibers, which were fewer in the pyloric than in the oxyntic mucosa. The entire VIP nerve fiber population was found to also contain PHI. Immunoreactive NPY was found to occur in the VIP/PHI fibers (VIP/PHI/NPY fibers) in the smooth muscle and intramural ganglia of both rat and mouse and in the mucosa of the mouse. Mucosal VIP/PHI fibers in the rat did not contain any NPY-like material. Perivascular NPY fibers in both species and mucosal NPY fibers in the rat did not contain VIP or PHI. The mucosa harbored numerous GRP fibers and VIP/PHI (rat) or VIP/PHI/NPY (mouse) fibers, and a modest number of NPY (rat) and SP fibers. In the submucosa the peptide-containing nerve fibers were found mainly in the ganglia and around blood vessels. Blood vessels received a rich supply of NPY fibers; the number of perivascular VIP/PHI, GRP, and SP fibers was much lower by comparison. The smooth muscle and myenteric ganglia harbored not only VIP/PHI/NPY, GRP, and SP fibers but also enkephalin, somatostatin, and cholecystokinin fibers. Gastrin-releasing peptide, VIP/PHI/NPY, SP, and enkephalin nerve cell bodies occurred in the myenteric ganglia. As studied in the rat, vagal denervation did not affect the density and distribution of the various peptide-containing nerve fibers. After sympathectomy, mucosal and perivascular NPY fibers disappeared. The other types of peptide-containing nerve fibers were not affected.
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PMID:Peptide-containing nerve fibers in the stomach wall of rat and mouse. 240 58

The effects of injecting ATP, ADP, AMP, adenosine and adenine intrathecally on the pain response induced by the injection of substance P (10 ng/mouse) intrathecally were studied. All the compounds except adenine inhibited the pain response in a dose-related manner. The ED50 values of ATP, ADP, AMP and adenosine were 2.10, 0.93, 0.88 and 0.48 micrograms/mouse, respectively. Pretreatment with theophylline at a dose of 100 mg/kg p.o. markedly diminished all the antinociceptive effects. The effect of adenosine was not affected by s.c. injection of naloxone. These results suggest the existence of adenosine receptors which modulate spinal nociceptive sensory processing, independently of the endogenous opiate system.
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PMID:Spinal antinociceptive effects of adenosine compounds in mice. 244 Jul 5

The behavioural response to intrathecally injected substance P (SP, 1.25 ng) was investigated in mice after lesioning of serotonergic (5-HT) pathways by intracerebroventricular 5,7-dihydroxytryptamine (5,7-DHT, 80 micrograms base/mouse) and after 5-HT synthesis inhibition by p-chlorophenylalanine (PCPA, 400 mg kg-1 for 6 consecutive days). Pretreatment with 5,7-DHT and PCPA reduced the 5-HT level in the spinal cord to 6 and 7% of controls and the noradenaline (NA) level to 69 and 84% of controls, respectively. Intrathecally injected SP produced a response consisting of vigorous biting, licking and scratching of the caudal part of the body. The response to SP was significantly increased 5 days after injection of 5,7-DHT, but only a non-significant tendency towards enhancement of the response was found after 24 h. There was no change in the response to SP 24 h after the last injection of PCPA. It is suggested that 5,7-DHT but not PCPA induces receptor supersensitivity to SP, and that reduction in spinal SP by 5,7-DHT may be a factor in this change in receptor sensitivity.
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PMID:Increased behavioural response to intrathecal substance P after intracerebroventricular 5,7-dihydroxytryptamine but not after p-chlorophenylalanine administration. 246 67

The innervation of cerebral blood vessels by nerve fibers containing calcitonin gene-related peptide (CGRP) and the vasomotor effects of this peptide are described for a number of different mammalian species. CGRP-immunoreactive nerve fibers were present in the adventitia of cerebral arteries in all species examined (guinea pig, cat, rabbit, rat, and mouse). Numerous perikarya containing CGRP immunoreactivity are demonstrable in the trigeminal ganglion of all species. In the cerebral perivascular nerve fibers and in trigeminal perikarya, CGRP is often colocalized with substance P and neurokinin A. Marked interspecies differences exist both in the density of CGRP-immunoreactive nerve fibers and in the cerebrovascular levels measured with radioimmunoassay. The highest concentrations were observed in cerebral vessels from guinea pigs, the lowest concentration in rabbit vessels, and intermediate levels in the feline and human cerebral vasculature. CGRP is a potent dilator of cerebral arteries in all species examined (human pial, feline middle cerebral, rabbit, guinea pig and rat basilar arteries). The concentration of CGRP eliciting half-maximal responses ranged from 0.4 nM (human pial artery) to 3 nM (rat and rabbit basilar arteries). Pretreatment of cerebral arteries with low concentrations of either substance P (0.1 nM) or neurokinin A (3 nM) attenuated slightly the CGRP-induced relaxations of guinea pig basilar arteries. Calcitonin was found to be a very weak dilator of cerebral arteries from human and guinea pig. Thus, cardiovascular nerve fibers containing CGRP appear to be present in all mammalian species (although to varying degrees) and CGRP is invariably a potent dilator of the cerebral arteries for all species.
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PMID:Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects. 350 Sep 57

In the tail-flick test in mice, the intraventricular administration of Substance P (10-5,000 ng/mouse) produced a naloxone-reversible analgesic effect of rapid onset and long duration. The dose-response curve was bell-shaped, the analgesic effect being smaller after the largest doses. The analgesia was blocked by concomitant intraventricular administration of the antibody against met-enkephalin but not by the antibody against beta-endorphin. In the hot plate assay, Substance P produced analgesia in mice with high sensitivity to pain, and hyperalgesia in mice with lower sensitivity to pain than normal. The analgesia was blocked by the antibody against met-enkephalin but the hyperalgesia or the scratching response were not modified by the antiserum. The results appear to indicate a dual effect, analgesic or hyperalgesic, of Substance P in mice, the former probably being mediated by release of met-enkephalin.
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PMID:Blockade by met-enkephalin antiserum of analgesia induced by substance P in mice. 618 74

The antinociceptive effects of intrathecally administered 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a potent 5-HT receptor agonist, were studied in three behavioral tests in mice: the tail-flick test and the intrathecal substance P and N-methyl-D-aspartic acid (NMDA) assays. Intrathecal administration of 5-MeO-DMT (4.6-92 nmol/mouse) produced a significant prolongation of the tail-flick latency. This action was blocked by 5-HT3 and gamma-aminobutyric acidA (GABAA) receptor antagonists but not by 5-HT2, 5-HT1A, 5-HT1B or 5-HT1S receptor antagonists. Binding studies indicated that 5-MeO-DMT had very low affinity for 5-HT3 receptors. 5-MeO-DMT inhibited biting behavior while increasing scratching behavior induced by intrathecally administered substance P. The inhibition of biting behavior was antagonized by intrathecal co-administration of 5-HT1B and GABAA receptor antagonists while 5-HT1A, 5-HT1S, 5-HT2 and 5-HT3 receptor antagonists had no effect. 5-MeO-DMT-enhanced scratching behavior was inhibited by all the antagonists used except ketanserin and bicuculline, suggesting the involvement of 5-HT1A, 5-HT1B, 5-HT1S, 5-HT3 and GABAA receptors. NMDA-induced biting behavior was inhibited by 5-MeO-DMT pretreatment; this action was antagonized by 5-HT1B, 5-HT3 and GABAA receptor antagonists. The involvement of these receptors in 5-MeO-DMT action suggests that it may promote release of 5-HT (5-hydroxytryptamine, serotonin).
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PMID:Intrathecal 5-methoxy-N,N-dimethyltryptamine in mice modulates 5-HT1 and 5-HT3 receptors. 750 56

The modulatory effect of spinal serotonin (5-HT)1 receptors on nociception was studied in mice. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone, putative 5-HT1A agonists, m-trifluoromethylphenyl-piperazine (TFMPP) and 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo(1,2-1a)quinoxaline (CGS 12066B), 5-HT1B agonists, and 5-carboxamidotryptamine (5-CT), a mixed 5-HT1A and 5HT1B agonist, were used. Intrathecal administration of 8-OH-DPAT, buspirone and 5-CT (1-12 nmol/mouse) significantly facilitated the tail-flick reflex, whereas TFMPP and CGS 12066B prolonged tail-flick latency. When administered i.t. after s.c. pretreatment (25 min) with morphine sulfate, 8-OH-DPAT, buspirone and 5-CT shifted the morphine sulfate dose-response curve 3- to 5-fold to the right. Spiperone, propranolol and pindolol (mixed 5-HT1A and 5-HT1B antagonists) effectively reversed both the tail-flick facilitation and the antagonistic effect on morphine sulfate-induced antinociception produced by 8-OH-DPAT and 5-CT. In addition, simultaneous i.t. administration of 8-OH-DPAT with substance P or N-methyl-D-aspartic acid decreased biting but increased scratching behavior, an effect which is also blocked by the 5-HT1 antagonists. These results confirm and extend other reports on the facilitory role of 5-HT1A receptor subtype on nociceptive responses and support the involvement of 5-HT1B receptor subtype in the antinociceptive action of serotonin.
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PMID:Differential roles of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptor subtypes in modulating spinal nociceptive transmission in mice. 768 14


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