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)

Radioimmunoassays of brain extracts have shown that several peptides occur in high concentrations in the CNS. The releasing-factor peptides TRF, LRF, somatostatin, CRF and GRF have the highest concentration in the hypothalamic extracts. High levels of somatostatin, CCK octapeptide, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) are found in cortical extracts. Substance P, CCK, NPY, and enkephalins are present in high concentrations in basal ganglia and mesolimbic areas. Pharmacological doses of these peptides result in several behavioural and vegetative effects. Immunocytochemical studies show that the CNS peptides are localised in neurones and in synaptic vesicles. In vitro studies with brain tissues show that peptides are capable of modifying the ongoing classical neurotransmission. In depressive patients several neuropeptides (CCK, CRF and NPY) have been shown to have low CSF levels. Patients dying of senile dementia have low cortical levels of somatostatin, CRF and substance P. In schizophrenic patients CCK peptides have shown to improve some symptoms. At present the therapeutic potentials of peptides are poorly known. More studies are required to understand their role in neurotransmission and related pathological states.
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PMID:Peptides and neurotransmission in the central nervous system. 282 29

Alzheimer's disease (AD) and senile dementia (SD) are often classified together, but there are genetic, biochemical, neuropathological and clinical arguments for separating them. The well-known Alzheimer lesions in the brains of patients with AD and SD are described, as is the loss of neurons in the locus coeruleus. White matter changes in brains from patients with dementia are discussed and related to AD and SD. Biochemical changes in brains of patients with AD and SD include reduced activity of acetylcholinesterase (AChE) and choline-acetyltransferase (CAT), indicating reduced activity in the acetylcholinergic system. There is also, however, reduced activity in the dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) system. The active amines are decreased while the end metabolites are decreased to a lesser extent or normal. The levels of the active amines are thought to reflect the number of neurons, while the levels of end metabolites reflect the rate of turnover in the system. 3-Methoxy-4-hydroxyphenylglycol (MHPG) is increased to levels above normal, which may indicate an increased rate of turnover in the NA system. Monoamine oxidase B (MAO-B), which is increased in advanced age, is further increased in patients with AD and SD. It is assumed that this enzyme is localized in extraneuronal tissue, and therefore the increase may reflect a gliosis. In brains from patients with AD and SD neuropeptides are also studied. Only somatostatin and substance P, however, seem to be reduced, indicating selective damage to the neuropeptides. The biochemical changes can be given pathogenetic importance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment. 286 36

The levels of specific neuropeptides and the activity of neuropeptidases known to degrade neuropeptides have been shown to be altered in senile dementia of the Alzheimer's type (SDAT) postmortem brain. We examined the metabolism of exogenous substance P, a neuropeptide with a putative role in SDAT pathology, in human postmortem temporal cortex, hippocampus, and caudate membrane homogenates from SDAT and sex- and age-matched control brain. The activity of two neuropeptidases known to metabolize substance P, neutral endopeptidase E.C.3.4.24.11 and metalloendopeptidase E.C.3.4.24.15, was also determined in the same postmortem, human tissue samples. The metabolic half-life of substance P was significantly increased in SDAT, postmortem, temporal cortex. The increased half-life of substance P was correlated with a decreased activity of the metabolic enzyme metalloendopeptidase 24.15 in temporal cortex. Substance P metabolism was not significantly altered in hippocampus or caudate tissues from SDAT brain compared to controls. The alteration of neuropeptidases demonstrated in this study and as shown by altered substance P metabolism may have a significant effect on the level of several biologically important neuropeptides in SDAT brain.
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PMID:Alterations of substance P metabolism and neuropeptidases in Alzheimer's disease. 754 30

Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.
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PMID:Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention. 824 6