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)

Levels of the neuropeptides substance P, somatostatin, and neurotensin were measured by radioimmunoassay in regions of the rat and human central nervous system (CNS) in aging. Somatostatin levels were significantly lower only in the corpus striatum of older rats. Substance P levels and neurotensin levels were generally stable with aging as were levels of somatostatin in regions other than the corpus striatum. In post-mortem human CNS tissues, no significant negative correlations of levels of the three peptides were observed with time to refrigeration or time to freezer for the samples. In the human CNS, there were no significant age-related alterations in substance P levels in frontal cortex, thalamus, hypothalamus, caudate nucleus, globus pallidus, or substantia nigra. There was a significant age-related decrease in substance P levels in the human putamen. This age-related decrease was not present in tissues from victims of Huntington's disease nor was there any striking difference in substance P levels as a function of duration of the disease. There were no significant age-related changes in somatostatin levels in human frontal cortex, caudate nucleus, putamen, medial globus pallidus, or substantia nigra. Among these same regions, there was a significant age-related decrease in neurotensin levels only in the pars compacta and pars reticulata of the human nigra. These, results implicate neuropeptides in aging processes in certain regions of the CNS. There are differences between rats and humans with respect to neuropeptides in the aging process in the CNS. Deterioration of some neuropeptide pathways in and to human basal ganglia may be involved in the suspected functional deterioration of parts of the extrapyramidal system in aging.
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PMID:A survey of substance P, somatostatin, and neurotensin levels in aging in the rat and human central nervous system. 617 78

In Huntington's disease, there is a decrease of the neuropeptides, substance P, enkephalins, and cholecystokinin in the striatonigral system, whereas in Parkinson's disease an increase of substance P is found in the substantia nigra. Several neuropeptides should be involved in Alzheimer's disease: substance P, endorphins, vasopressin, ACTH, somatostatin, vasoactive intestinal peptide, cholecystokinin, neurotensin, delta sleep-inducing peptide. Alterations of substance P, vasoactive intestinal peptide, cholecystokinin, somatostatin, and endorphins may be related to the pathophysiology of schizophrenia. Delta sleep-inducing peptide may interfere in addiction pathology.
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PMID:Putative peptide neurotransmitters in human neuropathology: a review of topography and clinical implications. 618 57

Using immunocytochemistry, this report visualizes immunoreactive substance P (SP) within human postmortem specimens of rostro-medial substantia nigra and dorsal spinal cord taken at autopsy from cases diagnosed as Huntington's disease (HD), and normal or non-HD. In the non-HD specimens of postmortem midbrain, the SP-immunoreaction products form a dense meshwork of neuronal processes throughout the substantia nigra (SN) pars compacta and pars reticulata. In the HD specimens, the SP-containing processes appear reduced. Presumably the reduced numbers of SP-containing processes result from the degeneration of parent SP perikarya located in the striatum, and cause the aberrant modulation of dopaminergic neurons which then influence basal ganglia output and therefore motor control. In the dorsal spinal cord substantia gelatinosa (SG), a nociceptive relay center, preliminary data demonstrate the reduced numbers of SP-containing processes in the HD cases compared with the non-HD cases. However neuronal degeneration is reportedly minimal in the spinal cord, and nociception in HD remains intact. Although the data require verification in SG, they suggest that certain kinds of neuronal degeneration may occur throughout the HD central nervous system. Additionally, the data imply that the role of SP in pain processing may require reevaluation.
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PMID:Substance P appears reduced in Huntington's disease: immunocytochemical findings in substantia nigra and substantia gelatinosa. 619 5

Huntington disease (HD) is an autosomal dominant hereditary disorder characterized by premature cell death, predominantly in the neostriatum. Decreased concentrations of several neurotransmitters and neuropeptides have been reported in the basal ganglia in Huntington disease. We now report that concentrations of radioimmunoassayable somatostatin are increased in extracts of the caudate (mean +/- standard error of the mean, ng/gm net weight; 247 +/- 24 versus 85 +/- 11), putamen (275 +/- 48 versus 74 +/- 11), external globus pallidus (100 +/- 10 versus 27 +/- 6), and internal globus pallidus (108 +/- 21 versus 21 +/- 8) in the disease. The concentrations of immunoreactive substance P measured in the same extracts were markedly reduced in caudate (mean +/- standard error of the mean, pmol/gm wet weight; 25 +/- 3 versus 109 +/- 20), putamen (28 +/- 7 versus 88 +/- 28), external globus pallidus (39 +/- 9 versus 196 +/- 62), and internal globus pallidus (60 +/- 17 versus 263 +/- 39), as well as in both subdivisions of the substantia nigra. Gel permeation chromatography and high-performance liquid chromatography showed radioimmunoassayable somatostatin to include peptides with physicochemical properties of the tetradecapeptide somatostatin and larger substances, including somatostatin-28-like material. A single peak of immunoreactive substance P corresponding to synthetic substance P was found by high performance liquid chromatography. These results suggest that immunoassayable somatostatin-containing neuronal elements in the neostriatum and globus pallidus in Huntington disease are affected differentially by the disease process from neurons that contain immunoreactive substance P.
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PMID:Somatostatin is increased in the basal ganglia in Huntington disease. 619 21

The distribution of substance P and leucine-enkephalin in selected regions of brain obtained postmortem from patients with Huntington's disease and from neurologically normal persons has been studied with immunocytochemical techniques. In the normal brain, substance P immunoreactivity was identified in medium-sized neurons in the neostriatum, in neurons of the external segment of the globus pallidus, and in fine fibers in teh neostriatum, inner segment of the globus pallidus, and in the pars reticulata of the substantia nigra. Huntington's disease brains all exhibited a marked decrease in substance P fiber density in the substantia nigra and globus pallidus. A few medium-sized neurons with substance P immunoreactivity remained in the neostriatal remnant. Leucine-enkephalin immunoreactive processes were present throughout the neostriatum of normal brain, and were densely packed in the external segment of the globus pallidus and in the substantia nigra. A uniform population of medium-sized neurons containing immunoreactive leucine-enkephalin was present in the caudate and putamen. By contrast, in the Huntington's disease brains there was a marked diminution of fiber staining in the globus pallidus and substantia nigra. A few medium-size neurons and sparse fibers with leucine-enkephalin immunoreactivity persisted in the atrophic neostriatum. These observations are consistent with previous reports of regional peptide concentrations in both normal and Huntington's disease brain. Cells containing substance P and leucine-enkephalin immunoreactivity persist in the basal ganglia in brains from patients with Huntington's disease, and we have no evidence that cellular content of one or the other peptide is associated with disproportionate cell death or survival.
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PMID:Immunocytochemical studies of substance P and leucine-enkephalin in Huntington's disease. 619 34

Chorea-acanthocytosis has been separated as a clinical entity different from Huntington's chorea, mainly based on the clinical findings, but the histopathological and biochemical features of chorea-acanthocytosis, especially of basal ganglia, have not been well established, because only two such autopsy cases have been reported. The case presented here was a 39-year-old man at autopsy, with 10 years duration of typical symptoms and signs of chorea-acanthocytosis. At autopsy, the abnormal histopathological findings in the central nervous system were mainly confined to the striatum, where the caudate nucleus and putamen showed severe and moderate atrophy, respectively. Morphometric evaluation of the numbers of small and large neurons in the striatum with the adjustment for the shrinkage produced in the disease processes was performed. The numbers of small neurons in the caudate nucleus and putamen were 1% and 20% of each control, respectively. On the other hand, the large neurons in the caudate nucleus showed a reduction of diameters without a decrease in number and those in the putamen showed a mild decrease in number. In the biochemical studies, marked decrease of substance P (SP) level without definite decrease of choline acetyltransferase and glutamic acid decarboxylase (GAD) activities in both caudate nucleus and putamen was found. Substantia nigra, where no evident histopathological abnormalities were found, showed definite decrease of GAD activity and SP level. In the peripheral nervous system, the lateral branch of deep peroneal nerve showed mild degree of axonal degeneration. Neurogenic muscular atrophy with severe and mild degrees was found in extensor digitorum brevis and quadriceps femoris muscles, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsy case of chorea-acanthocytosis. Special reference to the histopathological and biochemical findings of basal ganglia]. 620 44

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.
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PMID:Implications of neuropeptides in neurological diseases. 620 11

Huntington's disease (HD), a dominantly inherited disorder of the nervous system, is usually manifest about middle age by dance-like movements. The disorder may occur in children, when epilepsy and rigidity may be the predominant signs. Degeneration of neurons occurs throughout the whole brain, but this is most marked in the basal ganglia. Neurochemical examination of postmortem brain frozen at the time of autopsy has been collected from patients dying with HD and compared with postmortem brain from psychotic patients and cases without neuropsychiatric disease. A number of alterations in neurotransmitters and their biosynthetic enzymes have been found. There are decreased concentrations of the neuroinhibitory transmitter gamma aminobutyric acid and this is associated with increased concentrations of dopamine and serotonin in the basal ganglia. In addition, there is decreased activity of glutamic acid decarboxylase, choline acetyltransferase, angiotensin-converting enzyme, as well as a decreased concentration of the neuropeptide substance P. Various pharmacologic agents have been tried based on the neurochemical alterations, but nothing has been found to be superior to the various neuroleptics in common use.
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PMID:Chemical pathology of Huntington's disease. 644 56

Previous studies have shown that in advanced cases of Huntington's disease, enkephalin-immunoreactive striatal projections to the external globus pallidus may be more affected than substance P-containing striatal projections to the inner segment of the pallidum [Reiner A. et al. (1988) Proc. natn. Acad. Sci. U.S.A. 85, 5733-5737]. Other immunohistochemical [Ferrante R. J. et al. (1990) Soc. Neurosci. Abstr. 16, 1120] and neurochemical observations [Storey E. and Beal M.F. (1993) Brain 116, 1201-1222] suggest no difference in the loss of these peptide-containing pathways in Huntington's disease. In view of the potential significance of this issue for understanding the neuropathological process in Huntington's disease, we examined the globus pallidus in control and Huntington's disease brains, using a quantitative approach which involved high resolution image analysis of 7 microns frozen sections to determine the overall density of peptide-immunoreactive terminals. Results showed that in the controls there was no significant difference between the density of enkephalin- and substance P-immunoreactive terminals in the external and internal globus pallidus, respectively. In all Huntington's disease brains, including grade 1 cases, enkephalin-immunoreactive terminals in the external globus pallidus were significantly reduced compared to substance P-positive boutons in the internal segment of the adjacent section. In comparison to controls, enkephalin immunoreactivity in all Huntington's disease cases was significantly lower; substance P-immunoreactive terminals in the internal globus pallidus were significantly lower than controls in some of the grade 2 cases and in the grade 3 cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for a preferential loss of enkephalin immunoreactivity in the external globus pallidus in low grade Huntington's disease using high resolution image analysis. 753 2

Micromolar concentrations of beta-amyloid (25-35) or substance P stimulated [3H]MK-801 binding in the presence of low concentrations of glutamate (1 microM) and glycine (0.02 microM). Unlike polyamines spermine and spermidine, neither beta-amyloid (25-35) nor substance P increased [3H]MK-801 binding in the presence of maximally stimulating concentrations of glutamate and glycine. 5,7-Dichloro-kynurenic acid, CGS-19755, and arcaine completely inhibited the stimulated [3H]MK-801 binding. There was an apparent decreased potency of the [3H]MK-801 binding inhibition curve for 5,7-dichlorokynurenic acid, but not CGS-19755 or arcaine, in the presence of either beta-amyloid (25-35) or substance P. The compounds do not appear to act through the strychnine-insensitive glycine binding site because neither beta-amyloid (25-35) nor substance P displaced [3H]glycine binding. Full-length beta-amyloid (1-40), up to 10 microM, did not stimulate [3H]MK-801 binding. Concentrations > 10 microM could not be tested because they formed large aggregate precipitates in the assay. The data indicate that beta-amyloid (25-35) or substance P does not stimulate [3H]MK-801 binding at either the N-methyl-D-aspartate, glycine, or polyamine binding sites. Furthermore, the nonpeptide substance P receptor (NK1) antagonist, CP-96,345, did not block beta-amyloid (25-35)- or substance P-stimulated [3H]MK-801 binding. Therefore, the effect is not due to an interaction between the substance P receptors and the N-methyl-D-aspartate receptor-operated ionophore. Finally, if these observations can be verified using single-channel recording techniques, they may have implications in the pattern of selective neuronal loss observed in patients with neurodegenerative processes such as Alzheimer's, Parkinson's, and Huntington's diseases.
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PMID:beta-Amyloid (25-35) or substance P stimulates [3H]MK-801 binding to rat cortical membranes in the presence of glutamate and glycine. 768 71


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