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(SP) immunoreactivity in the rat brain and spinal cord were measured by radioimmunoassay and studied to correlate with the analgesic effect induced by electroacupuncture (EA). The results showed following: (1) There was a significant elevation in SP levels sn the hippocampus, hypothalamus and striatum after 30 min of EA. There was a markedly fall in the spinal cord. Statistical analysis revealed a positive correlation between the EA effect and the SP content in hypothalamus, striatum and statistical analysis revealed a correlation. In the spinal cord. (p less than 0.01), while the SP content in the hippocampus exhibited a similar degree of elevation in non responsive and good responsive animals to EA stimulation. (2) SP levels in the hippocampus, hypothalamus and striatum were increased by electroacupuncture stimulation (3v). The frequency of 1.5Hz was no obvious difference as compared with 100Hz in the effects on brain SP content. (3) SP content in the spinal cord decreased only using electroacupuncture stimulations of combination of higher intensity (3v) and higher frequency (100 Hz). (4) This effect could be blocked by the naloxone (i.p) and LSD (icv), but icv injection of Met-enkephalin antibodies had no affects on them.
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PMID:[Relationship between the content of central substance P and the analgesic effect of electroacupuncture in rats]. 248 Jan 95

Membrane potential changes induced by 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA) and 1,1-dimethyl-4-phenyl piperazinium (DMPP) were recorded from nodose ganglia (NG) by the sucrose-gap method. An amount of 0.002-0.5 mumol of the depolarizing agent was injected into the superfusion stream to the ganglion. Responses to 5-HT were also evoked from superior cervical (SCG) and dorsal root ganglia (DRG). 5-Hydroxytryptamine elicited depolarizations of graded amplitude. Maximal responses were 4.5 +/- 0.4 mV in nodose ganglia compared to 2.2 +/- 0.2 mV in superior cervical and 0.6 +/- 0.1 mV in dorsal root ganglia (means +/- SEM). In nodose ganglia, GABA induced smaller maximal depolarizations than did 5-HT, similar to those evoked by DMPP; dopamine was a weak depolarizing agent while substance P was apparently inactive. The dose-response curve for 5-HT in nodose ganglia was parallel to that for 5-HT in superior cervical ganglia and significantly to the left (ED50 values 0.029 and 0.098 mumol). Curves for 5-HT and GABA in nodose ganglia were superimposable. The high sensitivity of nodose ganglia cells to 5-HT is briefly discussed. Analogues of 5-HT lacking a hydroxyl group at position 5 on the nucleus were relatively inactive as depolarizing agents. Picrotoxin (10(-6)-10(-5) M) reduced or suppressed responses in nodose ganglia to GABA, whereas responses to 5-HT and DMPP were not much affected or, in the case of 5-HT, sometimes somewhat reduced. Quipazine (10(-6) M) was a selective antagonist of 5-HT responses in nodose ganglia; those to GABA and DMPP were not significantly altered. Neither trazodone nor LSD displayed antagonist properties at 5-HT receptors in nodose ganglia.
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PMID:Depolarizing responses recorded from nodose ganglion cells of the rabbit evoked by 5-hydroxytryptamine and other substances. 706 7

In the isolated spinal cord of the newborn rat, methysergide and LSD-25 depressed the monosynaptic reflex discharge selectively. Cyproheptadine and dimethothiazine did not inhibit the monosynaptic reflex. The selective inhibitory effect of methysergide on the monosynaptic reflex was not due to a presumptive low safety factor of this reflex. The inhibition was restored under a condition such as the compound action potential in the dorsal root was enhanced by 4-aminopyridine. Methysergide did not decrease the sensitivity of the motoneuron to substance P and L-glutamic acid. It is suggested that methysergide acts at the presynaptic terminal of Ia afferent fibers and depresses evoked transmitter release.
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PMID:Selective inhibition by methysergide of the monosynaptic reflex discharge in the isolated spinal cord of the newborn rat. 717 97

The 5-HT receptor mediating postjunctional relaxation of precontracted guinea-pig ileum has been characterized using several agonists and antagonists. Substance P precontracted tissues were potently relaxed by 5-HT (5-hydroxytryptamine, serotonin), 5-CT (5-carboxamidotryptamine) and several other indoles. The rank order of potency, with pEC50 values in parentheses, was 5-CT (7.6) > 5-methoxytryptamine (5.7) > 5-HT (5.5) > alpha-methyl-5-HT (4.7) > 2-methyl-5-HT (< 4.0) = tryptamine (< 4.0) = N,N-dimethyl-tryptamine (< 4.0) = N,N-dimethyl-5-HT (< 4.0) = dipropyl-5-CT (< 4.0) = sumatriptan (< 4.0). 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) acted as a potent (6.3), but partial, agonist with respect to 5-HT. The responses to 5-CT were antagonized by several compounds with the following rank order of affinity, with pKB values in parentheses: LSD (lysergic acid diethylamide; 8.1) = mesulergine (7.8) > methysergide (7.6) = spiperone (7.6) > clozapine (7.3) >> (-)-pindolol (< 6.0) > ketanserin (< 6.0) = ondansetron (< 6.0) = GR 113808 ([1-(2-methane-sulphonamido-ethyl)-piperidin-4-yl]-methyl-in dole-3- carboxylate maleate; < 6.0). The relaxant responses to 5-HT were also resistant to tetrodotoxin. These data are consistent with a functional 5-HT receptor, mediating relaxation of guinea-pig ileum, which exhibits an operational profile similar to that of the cloned guinea-pig 5-ht7 receptor. This study, therefore, provides evidence for a functional correlate of the 5-ht7 gene product.
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PMID:Characterization of a postjunctional 5-HT receptor mediating relaxation of guinea-pig isolated ileum. 856 92

Substance P antagonists have been proposed to be a new class of antidepressants. The present study aimed to determine the effect of the selective non-peptide rat neurokinin-1 (NK1) receptor antagonists WIN 51,708 and CP-96,345 on the firing activity of rat dorsal raphe serotonin (5-HT) and locus coeruleus noradrenaline (NA) neurons. While WIN51,708 (2mg/kg, i.v.) and CP-96,345 (0.15 mg/kg, i.v.) did not modify the firing activity of 5-HT and NA neurons, both antagonists attenuated the suppressant effect of the alpha2-adrenoceptor agonist clonidine on the firing activity of both types of neurons. In contrast, the responsiveness of 5-HT neurons to the i.v. administration of the 5-HT autoreceptor agonist LSD and the 5-HT1A receptor agonist 8-OH-DPAT remained unchanged. These findings suggest that NK1 receptor antagonists affect markedly the NA system via an attenuation of the function of alpha2-adrenoceptors on the cell body of NA neurons and, consequently, may also modulate 5-HT neurotransmission.
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PMID:Effect of neurokinin-I receptor antagonists on the function of 5-HT and noradrenaline neurons. 1081 15

Over the last 10 years or so in Europe, there has been a development of the "ecstasy" phenomenon, which is the symbol of "recreational" drugs in general. Users, either alone or in private parties, are on the increase. The phenomenon is most frequent in England and in the Netherlands, with an estimated incidence of 13-18% amongst the 18-25 years old, which may reach 52% in "exposed populations", such as individuals who go to "techno" night clubs. In France, the prevalence is uncertain, but estimated at least 5% of males between 18 and 23 years old. Several substance, with more or less the same effects, are grouped together by the term "ecstasy", the best-known one being 3,4-methylenedioxymethamphetamine (MDMA), but there are also an N-demethylated derivative (MDA), methylenedioxyethylamphetamine (MDEA), N-methyl-benzodioxazolylbutanamine (MBDB) and 4-bromo-2,5-dimethoxyphenylethylamine (2-CB or Nexus). The psychopathological consequences of MDMA in man are relatively poorly understood. On the basis of series of cases reported in the literature, acute psychosis, chronic psychosis similar to paranoid delusions, flash-back phenomena similar to with LSD, anxiety/panic states and depressive mood disorders may occur. The case which we report is therefore that of an acute psychotic episode, with residual symptomatology 6 months later, which occurred suddenly following absorption of toxic substances (alcohol and ecstasy), at least 12 hours after taking the ecstasy tablet without his knowing it, in an individual without any previous psychopathology, other than moderate social phobia. Twelve cases of acute psychotic episodes after ecstasy have been reported in the literature. Two of them occurred after a single dose and one after 2 doses. No author was able to examined the previous history of the individuals accurately, nor any possible psychopathological history. Our patient did not have any previous history of psychosis, using a standardized validated interview, which his peers and family confirmed. He did however fulfil the criteria of "social phobia". Retrospectively, we noted the extent of his psychomotor disinhibition with ecstasy, which seemed to be proportional to the intensity of his previous social inhibition. This point does not explain the psychotic episode. From a neurobiologic point of view, acute psychotic disorders are often related to dysfunction of the mesolimbic dopaminergic system. During the first 3 hours, the effect of absorption of MDMA is a massive release of the serotonin, dopamine and noradrenaline stocks. Later, an acute hyposerotoninergic state is present. In our observation, the psychotic disorder appeared at least 12 hours after taking ecstasy, during the reduction phase of the intoxication. Toxicological analysis of the blood was negative (this detection is only positive for 24 hours). Like other authors, our hypothesis is that serotoninergic dysregulation affects the dopaminergic system. Sudden disappearance of serotoninergic feedback on the dopaminergic pathways, may contribute to an increase in the mesolimbic hyperdopaminergic state. In animals, it has been shown that serotonin depletion induced by MDMA, unmasks the effects of a hyperdopaminergic state. In addition, although it has not been mentioned much in the literature, MDMA disturbs dopaminergic function either directly, or through the peptidergic systems (neurotensin, substance P, dynorphines). A consistent series of arguments therefore suggest that there is a sudden central hyperdopaminergic state, which may be related to the appearance, sometimes de novo, of an acute psychotic disorder. From the published cases, psychotic disorders following absorption of ecstasy, appear to become chronic. Most of the cases occurred in individuals, who either abused multiple substances or were chronic ecstasy users. In a case like the one we report, in an individual with good general health, who is not a drug user and who has an acute episode following a single dose, the prognosis should be good. Similarly, a team from Milan has described the experience of 3 friends who had a brief psychotic episode, following ingestion of substances containing ecstasy. These episodes resolved completely, after rehydration and anxiolytic treatment. However, after 6 months' follow-up, our patient still has psychotic symptoms, albeit mild, but which were not present before the intoxication. The patient and his psychiatrist do not envisage changing or stopping his antipsychotic treatment. Other authors have described a lesion in the serotoninergic neurons, by making a parallel with toxic effects described in animals, in particular in primates, with MDMA. Degradation of the serotoninergic cell bodies and nerve endings has been suggested to occur with high doses and/or repeated doses of MDMA. Other authors show the large variations in MDMA and MDA metabolism. (ABSTRACT TRUNCATED)
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PMID:[A case of acute psychotic episode after a single dose of ecstasy]. 1140 74

The objective of the study was to evaluate the distribution of substance P-immunoreactive nerve fibers in osteoarthritis knee and to determine whether a degenerative disease has any influence on the occurrence of neuropeptide-containing fibers, positively stained for substance P. Twenty consecutive patients, 16 females and 4 males, with gonarthrosis participated in the study. For comparison we used the group of 20 patients, 14 females and 6 males, operated on because of traumatic lesion of the knee. The medial and lateral retinaculum, medial compartment synovium and infrapatellar fat pad of these two groups of patients were evaluated using monoclonal antibody to substance P (PEPA40, Serotec Ltd, UK). The slices were examined semi-quantitatively for nerve fibers showing substance P expression. The values were analyzed with ONE WAY ANOVA test, which was then corrected with LSD test, at the level of significance p<0.05. There were no statistical differences in distribution of substance P nerve fibers in the fat pad, lateral and medial retinaculum or synovium between both groups, as well as in the each study group (p<0.05). The results allow us to speculate that different biomechanical axial disturbances of the knee could have the same influence on substance P-positive mechanoreceptors of the soft tissues around the joint modulating the pain pathway in knee osteoarthrosis.
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PMID:Distribution of substance P nerve fibers in osteoarthritis knee joint. 1647 80