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 in vivo microdialysis technique was used to study the effects of carboxyl or amino terminal sequences of substance P on the extracellular concentrations of dopamine, its metabolites dihydroxyphenylacetic acid and homovanillic acid, as well as on 5-hydroxyindoleacetic acid, in neostriatum and nucleus accumbens of freely moving rats. The i.p. administration of 37 nmol/kg of the substance P C-terminal heptapeptide analog [pGlu5, MePhe8, Sar9]SP5-11 (DiMe-C7) caused an increase in extracellular dopamine concentrations in nucleus accumbens but not in neostriatum. The administration of the equimolar dose of the heptapeptide N-terminal fragment substance P 1-7 (SP1-7) did not have an effect in either structure. No changes were observed in the extracellular concentrations of the metabolites after the administration of either substance. These results are discussed with respect to the reinforcing effects of substance P and its C-terminal sequence, which may be mediated via dopamine release in the nucleus accumbens.
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PMID:The C-terminal fragment of substance P enhances dopamine release in nucleus accumbens but not in neostriatum in freely moving rats. 128 May 16

Peripheral nerve lesions cause retrograde changes in the spinal cord, involving initially the descending serotoninergic pathways and later the substance P sensory input and methionine-enkephalin interneurons. Within 48 h after sciatic nerve resection there is a significant increase of 5-hydroxyindoleacetic acid in the lumbar spinal cord with no changes of serotonin metabolism in the cell body areas. The immunocytochemical analysis of the spinal cord shows that 20 days after nerve lesion there is a loss of substance P-positive boutons in the laminae I and II of the dorsal horn in the lumbar segment. Such a morphological change is correlated by radioimmunoassay for substance P and methionine-enkephalin, that reveals a significant loss of both peptides. Treatment with acetyl-L-carnitine prevents the early 5-hydroxyindoleacetic acid increase and the reduction of peptide content observed 20 days after lesioning the sciatic nerve. These data suggest that treatment with acetyl-L-carnitine exerts a neuroprotective activity preventing the retrograde changes triggered by peripheral nerve lesions.
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PMID:Intraspinal degenerative atrophy caused by sciatic nerve lesions prevented by acetyl-L-carnitine. 128

The neurohumoral mechanisms behind the pain-suppressing effect of dorsal column stimulation (DCS) still remain obscure. Experimental observations have indicated an inhibitory role for serotonin and, under certain conditions, also for substance P (SP), on nociceptive transmission in the spinal cord. Furthermore, some observations suggest that these substances might be involved in the effect of DCS. The present series of experiments was undertaken to investigate whether serotonin and SP are released in the dorsal horn by DCS. Twenty-one adult cats, in some experiments anesthetized, in others decerebrated at the midcollicular level, were used. Microdialysis probes were implanted bilaterally in lumbar dorsal horns (L5-L7) and perfused with Krebs' solution. Dialysates were analyzed for serotonin by high-performance liquid chromatography or for SP by radioimmunoassay. DCS was applied at the thoracolumbar junction with current parameters similar to those used clinically in humans. DCS induced a significant release of serotonin in the dorsal horn of decerebrated animals (173 +/- 83% increase; mean +/- standard error; n = 4; P less than 0.01), whereas the levels of the metabolite 5-hydroxyindoleacetic acid were not significantly influenced. In contrast, no release of SP could be recorded in response to DCS in the decerebrated preparation, although peripheral nociceptive stimulation (pinch) and noxious electric dorsal root stimulation induced an elevation of the SP levels. However, in intact animals DCS provoked a marked SP release in the dorsal horn (190 +/- 92% increase; n = 7; P less than 0.01). The release of serotonin and SP after DCS may indicate that these substances participate in the mediation of the pain alleviating effect of DCS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dorsal column stimulation induces release of serotonin and substance P in the cat dorsal horn. 138 Oct 66

The cerebrospinal fluid (CSF) concentrations of thyrotropin-releasing hormone (TRH), substance P (SP), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were measured in 15 consecutive patients with the sleep apnea syndrome (SAS) and in healthy control subjects. Second measurements were performed 6 months after surgical treatment in 10 of the patients. The mean (+/- SD) concentration of TRH-like immunoreactive material (TRH-LIM) (pg/ml) did not differ significantly between patients with SAS (8.1 +/- 2.8) and control subjects (7.5 +/- 2.2). However, postoperatively, this concentration was increased in the six clinically cured patients with SAS, from 6.9 +/- 2.7 to 9.4 +/- 1.6 (p less than 0.03). Substance P-like immunoreactive material (SP-LIM) was higher in untreated patients with SAS than in control subjects: 19.2 +/- 6.7 versus 14.4 +/- 4.2 fmol/ml (p less than 0.02), and the level remained high after operation in the group treated surgically. The HVA, 5-HIAA, and MHPG concentrations were similar in patients with SAS and control subjects, and no consistent changes were found postoperatively. The CSF deviations in TRH-LIM and SP-LIM concentrations in the patients may reflect a primary central nervous system defect or they may be secondary to intermittent nocturnal hypoxia, progressive hypercapnia, and/or sleep fragmentation. In this sense, both these systems may be markers of SAS-SP as a "trait" marker and TRH as an indicator of the current state.
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PMID:Substance P, thyrotropin-releasing hormone, and monoamine metabolites in cerebrospinal fluid in sleep apnea patients. 138 67

Seasonal affective disorder is a form of depression which recurs at the same time of the year. Exposure to bright artificial light at a dose of 2,500 lux is used to treat seasonal affective disorders. We exposed a pigmented (Brown Norway) and a nonpigmented (Sprague-Dawley) rat strain with bright artificial light for 21 days at two doses (2,500 and 6,100 lux) and analyzed dopamine, dihydroxyphenyl-acetic acid, 5-hydroxytryptamine (5-HT), and 5-hydroxyindole-acetic acid (5-HIAA) by high performance liquid chromatography (HPLC) and electrochemical detection in eight different brain regions. Furthermore, we measured tissue levels of substance P (SP), neurokinins (NK), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) with radioimmunoassay. Our data obtained with light microscopy show that bright artificial light at both doses induced a massive destruction of photoreceptors in the retina of albino rats but not of the pigmented rat strain. Retinal lesion of photoreceptors resulted in increased tissue levels of all measured neuropeptides except SP in the hypothalamus and increased VIP in the ventral tegmental area/substantia nigra. Furthermore, increased 5-HT and 5-HIAA tissue levels were found in the ventral tegmental area/substantia nigra. In contrast, in the frontal cortex there was a significant reduction in 5-HIAA tissue levels and a decreased 5-HIAA/5-HT ratio, indicating decreased 5-HT metabolism. Light exposure of the pigmented rat strain revealed no changes in the measured biogenic amines and neuropeptides in any investigated brain region. Our data suggest that retinal lesion but not direct visual neurotransmission induced changes in neurotransmitters in some brain regions. We conclude that Brown Norway rats but not Sprague-Dawley rats are useful to study neurochemical effects of bright artificial light. However, Sprague-Dawley rats may be a useful tool to study biochemical mechanisms of photoreceptor damage by bright light.
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PMID:Effects of bright artificial light on monoamines and neuropeptides in eight different brain regions compared in a pigmented and nonpigmented rat strain. 152 5

1. The effects of 5-hydroxytryptamine3 (5-HT3) receptor antagonists on the behavioural hyperactivity response which results from injection of the neurokinin receptor agonist [pGlu5, MePhe8, Sar9]-substance P (5-11) (DiMe-C7) into the ventral tegmental area (VTA) of the rat midbrain have been determined. 2. Subcutaneous administration of ondansetron (GR38032) (0.001-0.3 mg kg-1), GR65630 (0.01 mg kg-1), ICS 205-930 (0.1 mg kg-1) and MDL 72222 (0.1 mg kg-1), inhibited the DiMe-C7-induced hyperactivity response. 3. The effects of ondansetron on DiMe-C7-induced changes in dopamine and 5-HT metabolism in discrete areas of rat forebrain were studied in order to investigate further the possible mechanism of action of 5-HT3 antagonists in modifying mesolimbic dopaminergic systems. 4. Intra-VTA administration of DiMe-C7 increased levels of dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens, olfactory tubercules and right amygdala, indicating increased mesolimbic dopamine metabolism. DOPAC levels were not significantly increased in the frontal cortex, left amygdala or striatum. Dopamine levels were not altered in any of these brain areas. DiMe-C7 also increased 5-hydroxyindoleacetic acid (5-HIAA) levels in the amygdala but this was only statistically significant in the right amygdala. 5-HT levels were not changed significantly by DiMe-C7 treatment. 5. In control rats, pretreatment with ondansetron (0.1 mg kg-1) had no effect on the levels of dopamine, 5-HT or their metabolites, but in rats given DiMe-C7, ondansetron significantly inhibited the increase in DOPAC levels in the nucleus accumbens. 6. These results are in agreement with the proposed facilitatory role of 5-HT3 receptor activation on mesolimbic dopaminergic transmission, and suggest that 5-HT3 antagonists may have important therapeutic indications for the treatment of CNS disorders in which mesolimbic dopamine systems are perturbed.
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PMID:Effect of 5-HT3 receptor antagonists on responses to selective activation of mesolimbic dopaminergic pathways in the rat. 169 72

A depletion of large cholinergic neurons in the nucleus basalis of Meynert is a consistent finding in Alzheimer's disease (AD). The nucleus basalis of Meynert also contains interneurons and afferents that may modulate its functioning. In the present study we examined neurochemical markers for neuropeptides, amino acid neurotransmitters, and monoaminergic neurotransmitters in postmortem samples of the nucleus basalis in 16 control subjects and 30 patients with AD. There were no significant changes in glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and catecholamines; however, concentrations of serotonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol were significantly reduced. Choline acetyltransferase activity was significantly reduced, consistent with previous reports. Galanin immunoreactivity was significantly increased twofold in the patients with AD, but there were no significant changes in substance P, somatostatin, or neuropeptide Y immunoreactivity. Since galanin inhibits acetylcholine release, and produces cognitive deficits in animals, increased galanin immunoreactivity in the nucleus basalis of Meynert in AD may contribute to the cognitive deficits that characterize the illness.
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PMID:Galanin immunoreactivity is increased in the nucleus basalis of Meynert in Alzheimer's disease. 169 71

We previously found a relative sparing of somatostatin and neuropeptide Y neurons 1 week after producing striatal lesions with NMDA receptor agonists. These results are similar to postmortem findings in Huntington's disease (HD), though in this illness there are two- to threefold increases in striatal somatostatin and neuropeptide Y concentrations, which may be due to striatal atrophy. In the present study, we examined the effects of striatal excitotoxin lesions at 6 months and 1 yr, because these lesions exhibit striatal shrinkage and atrophy similar to that occurring in HD striatum. At 6 months and 1 yr, lesions with the NMDA receptor agonist quinolinic acid (QA) resulted in significant increases (up to twofold) in concentrations of somatostatin and neuropeptide Y immunoreactivity, while concentrations of GABA, substance P immunoreactivity, and ChAT activity were significantly reduced. In contrast, somatostatin and neuropeptide Y concentrations did not increase 6 months after kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) lesions. At both 6 months and 1 yr, QA lesions showed striking sparing of NADPH-diaphorase neurons as compared with both AMPA and KA lesions, neither of which showed preferential sparing of these neurons. Long-term QA lesions also resulted in significant increases in concentrations of both 5-HT and 5-hydroxyindoleacetic acid (HIAA), similar to findings in HD. Chronic QA lesions therefore closely resemble the neurochemical features of HD, because they result in increases in somatostatin and neuropeptide Y and in 5-HT and HIAA. These findings strengthen the possibility that an NMDA receptor-mediated excitotoxic process could play a role in the pathogenesis of HD.
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PMID:Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. 171 Jun 57

The spinal motor effects of galanin, which co-exists with 5-hydroxytryptamine (5-HT) and thyrotrophin-releasing hormone (TRH) in bulbospinal raphe neurones innervating spinal motoneurones, were examined by administering this neuropeptide through indwelling intrathecal cannulae to conscious adult Wistar rats. The acute effect of intrathecal galanin on spontaneous motor behaviour and the motor behaviours (back muscle contractions and wet-dog shakes) elicited by intrathecal injection of the non-selective 5-HT receptor agonist, 5-methoxy-N, N'-dimethyltryptamine (5-MeODMT) or the TRH analogue, RX 77368 analogue, RX 77368 (pGlu-His-3,3'-dimethyl-ProNH2), respectively, and the chronic effect of galanin on neurochemical markers for bulbospinal raphe neurones and spinal motoneurones were determined. Intrathecal galanin (0.1 to 10 micrograms) did not produce any notable motor behaviours when given alone, but pretreatment with the neuropeptide (0.1 micrograms) significantly attenuated both the number of wet-dog shakes and the amount of forepaw-licking induced by RX 77368, without affecting 5-MeODMT-induced back muscle contractions. Repeated intrathecal galanin administration (1 microgram, twice daily for 5 d) significantly elevated 5-HT (but not 5-hydroxyindoleacetic acid) and substance P-like immunoreactive (LI) levels and choline acetyltransferase (ChAT) activity in the dorsal, but not in the ventral, portion of the thoraco-lumbar spinal cord. In contrast, chronic intrathecal galanin did not alter the TRH- or calcitonin gene-related peptide (CGRP)-LI levels in either spinal cord region.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic effects of intrathecal galanin on behavioural and biochemical markers of spinal motor function in adult rats. 171 12

A biochemical model of chronic trigeminal facial pain with elevated substance P (SP) and co-dysfunctional dopamine (DA), norepinephrine (NE) and purinergic systems is proposed. The serotonergic system is hypoactive as judged by low 5 hydroxyindoleacetic acid (5HIM). In distinction, intracerebral opioids may not be dysfunctional in facial pain as measured by normal levels of beta endorphin (BE). The neuropeptides somatostatin (SOM), cholecystokinin (CCK), met and leu-enkephalin (MENK, LENK) have very small picogram concentrations in these pain patients, but no definite conclusion can be reached on their role in trigeminal pain, alone or with monoamines, because of the small numbers, both sample size and concentrations. Interpretive obstacles to such human neurochemical studies suggest that future work might move to human clinical trials comodulating SP down, inhibitory peptides (SOM, CCK) up, and enhancing monoamine systems.
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PMID:Trigeminal facial pain: a model of peptides and monoamines in intracerebral cerebrospinal fluid. 172 75


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