Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously found that quinolinic acid striatal excitotoxin lesions result in a relative sparing of somatostatin and neuropeptide Y neurons. In the present study we examined dose-response effects of excitotoxins acting at the three subtypes of glutamate receptors: N-methyl-D-aspartate (AA1), quisqualate (AA2), and kainic acid (AA3). Concentrations of both somatostatin-like immunoreactivity (SLI) and neuropeptide a Y-like immunoreactivity (NPYLI) were compared with those of substance P-like immunoreactivity (SPLI) and GABA. Kainic acid (AA3), quisqualic acid (AA2), and AMPA (AA2) resulted in dose-dependent reductions in all four neurochemical markers examined, while N-methyl-D,L-aspartate (AA1) and quinolinic acid (AA1) resulted in relative sparing of SLI and NPYLI. At doses of each excitotoxin which resulted in comparable 50% reductions in both GABA and SPLI only N-methyl-D,L-aspartate and quinolinic acid had no significant effect on concentrations of SLI and NPYLI. The relative sparing of somatostatin-neuropeptide Y neurons was confirmed histologically by using histochemical staining for NADPH-diaphorase neurons combined with either Nissl stains, or immunohistochemical staining for enkephalin. Lesions with N-methyl-D-aspartate agonists resulted in preferential sparing of NADPH-diaphorase neurons while these neurons were more vulnerable than other neurons to kainic acid or AMPA. Choline acetyltransferase neurons were relatively spared, as compared with other neurons, by agents acting at all three glutamate receptor subtypes. N-methyl-D,L-aspartate lesions were blocked with MK-801, while there was no effect on quisqualic acid or kainic acid lesions. The relative sparing of somatostatin-neuropeptide Y neurons following striatal excitotoxin lesions with N-methyl-D-aspartate (AA1) agonists probably reflects a paucity of AA1 receptors on these neurons. Since these neurons are also spared in Huntington's disease, excitotoxins acting at the N-methyl-D-aspartate (AA1) site provide an improved neurochemical model of this illness.
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PMID:Differential sparing of somatostatin-neuropeptide Y and cholinergic neurons following striatal excitotoxin lesions. 256 16

Immunocytochemical studies of the distribution and intensity of Substance P and Met-enkephalin staining in the basal ganglia and substantia nigra were carried out in five cases each of brains from patients with Huntington's disease, Parkinson's disease, Alzheimer's disease, and normal controls. The usefulness of the peroxidase-antiperoxidase method for human autopsy material was confirmed. Substance P and Met-enkephalin fibers were distributed in essentially the same pattern as described in experimental animals and in human brains. In Huntington's disease brains decreased Substance P staining was found in the internal globus pallidus and the substantia nigra, in agreement with radioimmunoassay studies by others. Met-enkephalin staining in the external globus pallidus was of normal intensity, although present within a shrunken area. In Parkinson's and Alzheimer's diseases there was intense immunoreactivity for Substance P in the globus pallidus and substantia nigra, and for Met-enkephalin in the globus pallidus, at variance with reported decreases in Parkinson's disease by radioimmunoassay, but in essential agreement with other immunocytochemical studies. Immunocytochemical methods complement radioimmunoassays of human brain and may help in mapping neuropeptidergic pathways and in pinpointing abnormalities in these pathways in basal ganglia disorders.
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PMID:Immunocytochemical studies of substance P and Met-enkephalin in the basal ganglia and substantia nigra in Huntington's, Parkinson's and Alzheimer's diseases. 257 85

The study of neurotransmitter receptors aids in the understanding of the normal anatomy, pharmacology, therapeutics and pathophysiology of disease processes involving the basal ganglia. Receptors may be studied in vitro by homogenate binding experiments, enzyme analysis or quantitative autoradiography and in vivo with positron emission tomography. In the substantia nigra (SN), receptors have been identified for somatostatin, neurotensin, substance P, glycine, benzodiazepine and GABA, opiates, dopamine, angiotensin converting enzyme (ACE) and serotonin. The striatum has receptors for dopamine, GABA and benzodiazepines, acetylcholine, opiates, substance P, glutamate and cholecystokinin. GABA and benzodiazepine receptors are also located in the globus pallidus. In Parkinson's disease, striatal dopamine D-2 receptors are elevated in patients that have not received L-DOPA therapy. This supersensitivity is reversed with agonist therapy. Muscarinic binding to cholinergic receptors seems to correlate with dopamine receptors. Delta opiate receptors are increased in the caudate and mu binding is reduced in the striatum. In the SN of patients with Parkinson's disease, there is reduced binding of somatostatin, neurotensin, mu and kappa opiates, benzodiazepine and GABA and glycine. In Huntington's disease, there is reduced binding of GABA and benzodiazepines, dopamine, acetylcholine, glutamate and CCK. There is increased binding of GABA in both the SN and globus pallidus. Glycine binding is increased in the substantia nigra and ACE is reduced.
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PMID:Receptors in the basal ganglia. 282 9

Neurotransmitter abnormalities in the basal ganglia of individual "choreic" patients (9 cases of Huntington's disease-HD and 3 cases of dentatorubropallidoluysian atrophy-DRPLA) and 14 normal controls were investigated. Choline acetyltransferase activity in the striatum was decreased in approximately half the "choreic" patients. GABA concentration in the substantia nigra or in the globus pallidus was decreased in all "choreic" cases except one case of DRPLA. Substance P concentration was also reduced in the same nuclei as GABA except in one case of HD. These findings imply: cholinergic, GABAergic or substance P-related markers found in the basal ganglia of HD are not disease-specific but also found in the other "choreic" disorder, i.e. DRPLA; most prominent biochemical changes in HD would be a decrease of GABA in the basal ganglia. Correlation analysis of the markers in the basal ganglia and the striatal neurone densities of "choreic" patients (5 cases of HD and 3 cases of DRPLA) and 7 normal controls yielded positive correlation between GABA concentration in the substantia nigra and the globus pallidus, and the neuronal cell density in "small" cells in the striatum of normal control and HD. Positive correlation between substance P concentration and the striatal neurone density was only found in the substantia nigra. Choline acetyltransferase activity in the striatum was found to be positively correlated with the density of "large" cells in the striatum rather than that of "small" cells. In DRPLA there was no direct correlation between the values of the markers in the basal ganglia and the striatal neurone density. The decrease of transmitter markers without striatal cell loss in this particular choreic disorder could be regarded as a sequence of "biochemical degeneration" of striatal neurones. Based on these findings, the underlying mechanisms of choreic involuntary movements were briefly discussed.
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PMID:Studies on neurotransmitter markers and striatal neuronal cell density in Huntington's disease and dentatorubropallidoluysian atrophy. 286 38

In the past twenty years, more than thirty peptides have been discovered to be present in the mammalian central nervous system (CNS). As the neuroanatomical distribution, neurochemical, electrophysiological and pharmacobehavioral effects of this novel group of neuroregulators have been described, it is evident that certain of these peptide-containing neural circuits may be pathologically altered in neuropsychiatric disorders. Although much attention has been focused on the opioid peptides, substantial data strongly support the hypothesis that non-opioid peptides such as somatostatin, neurotensin and substance P are altered in a diverse number of neuropsychiatric disorders including Alzheimer's disease, Huntington's chorea, Parkinson's disease, major depression and schizophrenia.
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PMID:Involvement of non-opioid peptides in the pathogenesis of neurological and psychiatric disorders: evidence from CSF and post-mortem studies. 293 45

Huntington's chorea is a degenerative disorder of the human brain characterized by a marked loss of intrinsic neostriatal neurons. This situation can be reproduced by kainic acid injection in the caudate nucleus. Activity of pars reticulata neurons ipsilateral to the injected neostriatum was studied in normal, control (saline-injected) and lesioned rats. They were identified by electrophysiological and histological criteria (Fig. 1). Results obtained in normal and control rats were very similar (Table I). As previously described, the mean frequency of these neurons was high. An important percentage (respectively 72.5 and 73%) and these neurons presented the characteristics of a regular firing pattern (so called "organized neurons"). Results obtained in kainic acid lesioned rats were significantly different (Table I). The mean frequency was lower and only 11% of reticulata cells remained organized after neostriatal lesion. This important dysfunction may be explained in various ways: The neostriato-nigral pathway's destruction involves both the inhibitory GABAergic tract and the excitatory substance P tract (GALE et al., 1978). Other inputs arising from many structures in the brain continue to exert their own action on SN neurons, resulting in an unbalance in the SN inputs. It is well known that the nigral dopamine influences the neuronal activity of pars reticulata neurons (Ruffieux et Schultz, 1980; Waszczak et Walters, 1983). Doudet et al. (1984 b) previously reported a dysfunction of neuronal activity of dopaminergic cells after striatal lesion. A disturbance in the electrical activity may induce a similar disturbance in the intranigral dendritic release of DA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activity of substantia nigra pars reticulata neurons after lesion of the ipsilateral neostriatum by kainic acid in rats]. 293 12

The regional distributions of substance P and Methionine-enkephalin (Met-enkephalin) were determined in normal human brains and in Huntington's disease using sensitive radioimmunoassays. Model experiments showed that both Met-enkephalin- and substance P-like immunoreactivities were stable for up to 72 h post-mortem in mouse brain. The results of high pressure liquid chromatography (HPLC) analyses indicated that the majority of the immunoreactivity detected in human globus pallidus corresponded to the native peptides, substance P or Met-enkephalin. In Huntington's disease the present results confirm that there is a substantial drop (> 80%) in the substance P content of the globus pallidus (both medial and lateral segments) and substantia nigra, and there was also a reduction (> 50%) in the Met-enkephalin content of these areas. This result suggests the loss of striato-pallidal and striato-nigral substance P and enkephalin-containing projections in Huntington's disease.
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PMID:Regional distribution of methionine-enkephalin and substance P-like immunoreactivity in normal human brain and in Huntington's disease. 615 54

Substance P (SP), a putative peptide neurotransmitter, was measured in human lumbar cerebrospinal fluid (CSF) by radioimmunoassay. Substance P-like immunoreactivity (SPLI) was present in the CSF of 18 neurologically normal adults in concentrations ranging from 2.9 to 11.1 fmol per milliliter, with a mean of 7.0 /+- 0.6 fmol per milliliter (mean /+- SE). Slightly more than half of the CSF-SPLI cochromatographed with synthetic SP on Sephadex G-25. There was no apparent gradient in CSF-SPLI concentration over the first 30 ml of CSF removed by lumbar puncture. Mean concentrations CSF-SPLI in patients with Huntington disease, parkinsonism, miscellaneous dyskinesias, progressive supranuclear palsy, myopathy, and amyotrophic lateral sclerosis did not differ significantly from normal. Patients with neuropathy or multiple-system atrophy (Shy-Drager syndrome) had significantly reduced mean CSF-SPLI concentrations. These observations suggest that lumbar CSF-SPLI arises largely from spinal cord, nerve roots, or dorsal root ganglia, and that pathologic processes affecting these structures may be reflected by reduced levels of CSF-SPLI.
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PMID:Substance P in human cerebrospinal fluid: reductions in peripheral neuropathy and autonomic dysfunction. 616 19

Substance P (SP) levels were determined by radioimmunoassay (RIA) in several regions of post-mortem brain of controls and Huntington's disease (HD) patients. In controls, highest SP levels were found in basal ganglia, substantia nigra and hypothalamus. Nigral pars reticulata contained 3--4-fold higher levels than pars compacta. In HD, SP levels were reduced in all basal ganglia and substantia nigra. The reductions ranged from 48% in caudate nucleus to over 90% in nigral pars reticulata. There were no changes in SP levels in HD frontal cortex, thalamus or hypothalamus.
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PMID:Reduction in basal ganglia and substantia nigra substance P levels in Huntington's disease. 616 36

Somatostatin, substance P, cyclic AMP and cyclic GMP were determined in the cerebrospinal fluid of patients with Huntington's disease, in first generation relatives of choreic patients and in neurological control patients. Substance P levels were not significantly altered, but somatostatin levels were markedly decreased both in affected patients and symptom-free offspring. Cyclic AMP was decreased only in patients with advanced stages of the disease while cyclic GMP was normal. Evidence is discussed which may support a role of somatostatin deficiency in the pathophysiology of chorea.
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PMID:Huntington's chorea-- measurements of somatostatin, substance P and cyclic nucleotides in the cerebrospinal fluid. 616 83


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