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)

Recent evidence indicates that, in addition to the involvement of cholinergic and other neurotransmitter systems, various neuropeptides that occur in cortical and subcortical brain regions have a role in cognitive behavior. This evidence results largely from behavioral studies in rodents and other animals, following peptide administration and only in a very few cases from similar studies in human subjects. Several neuropeptides studied appear to enhance or produce changes conducive to improvement in cognitive performance and these include vasopressin, corticotrophin-releasing hormone (CRH), somatostatin, substance P, neuropeptide Y, and thyrotrophin-releasing hormone (TRH), while one peptide, galanin, has been reported to inhibit cognitive processes. Of those neuropeptides that improve performance, only TRH has been shown recently to attenuate the memory impairment of human subjects and Alzheimer patients treated with an anticholinergic drug, and this review describes a series of complimentary studies in adult and aged rodents that contribute to our understanding of the possible mechanisms involved in the role of TRH in cognition.
 ...
PMID:Effect of neuropeptides on cognitive function. 931 49

Interleukin-6 (IL-6) is a proinflammatory cytokine whose synthesis is induced by a variety of stimuli including interleukin-1 (IL-1), substance P (SP), and histamine. Because IL-6 has been implicated in the etiopathology of different human diseases including multiple myeloma, rheumatoid arthritis, multiple sclerosis, acquired immunodeficiency syndrome dementia complex, and Alzheimer's disease, its inhibition may be of therapeutic interest. A main demand on an effective inhibitor of IL-6 expression is that it inhibits IL-6 synthesis independently of the inducing stimulus. We therefore used human astrocytoma cells to search for signal transduction cascades and transcription factors whose inhibition suppresses IL-6 synthesis after stimulation with three different inductors, IL-1beta, SP, and histamine. Whereas the antioxidant pyrrolidinedithiocarbamate was only able to inhibit IL-1beta-induced IL-6 expression, inhibition of protein kinase C prevented IL-6 expression induced by all three substances. Promoter deletion analysis revealed that IL-1beta-induced IL-6 expression required the transcription factor nuclear factor-kappaB (NF-kappaB), whereas SP- and histamine-induced IL-6 synthesis was essentially controlled by NF-IL-6. These findings suggest that inhibition of protein kinase C or a combinatory inhibition of NF-IL-6 and NF-kappaB binding are strategies to effectively suppress IL-6 synthesis. They therefore provide the basis for the development of antiinflammatory drugs used to treat disorders in which IL-6 is pathogenically involved.
 ...
PMID:Substance P and histamine induce interleukin-6 expression in human astrocytoma cells by a mechanism involving protein kinase C and nuclear factor-IL-6. 952 75

Impairment of the basal forebrain cholinergic system is an important change in the brains of Alzheimer's disease patients. Various neurotoxins have been used to achieve this in animal models. In this study the effects of chemical lesions by ibotenic acid (IBO), a glutamate analogue and by 192 IgG-saporin, a highly specific immunotoxin against cholinergic neurons, were investigated. The toxins were delivered stereotaxically into the brains of young Sprague-Dawley rats which were later sacrificed by decapitation. Choline acetyltransferase (ChAT) activity was measured by radioenzymatic assay and substance P (SP), neuropeptide Y (NPY) and somatostatin (SOM) levels by radioimmunoassay. Decreased ChAT and SOM levels were observed in the cortex and the hippocampus in both experiments. Cortical SP levels were increased after IBO lesions but were unaffected after 192 IgG-saporin lesions. NPY levels remained unchanged in both experiments. The results indicate that there were specific changes in neuropeptide contents in the cortex and hippocampus in response to cholinergic damage in the rat brain.
 ...
PMID:Cholinergic lesions of the rat brain by ibotenic acid and 192 IgG-saporin: effects on somatostatin, substance P and neuropeptide Y levels in the cerebral cortex and the hippocampus. 975 27

In an attempt to answer the question of whether or not the so-called tachykinin-like region of the Alzheimer beta-amyloid protein [Abeta(25-35)] can act as a tachykinin, the sequences Abeta(25-35), Abeta(25-35)amide and their norleucine-35 and phenylalanine-31 analogues were synthesized. These peptides were examined with ligand binding studies, electron microscopy, CD and NMR. In all cases some differences were found between the Abeta(25-35) analogue and the corresponding Phe31 peptide. In addition, in ligand displacement studies on tachykinin NK1 receptors, only the Phe31 analogue showed activity comparable to that of genuine tachykinins. We conclude that peptides based on Abeta(25-35) but with a Phe residue at position 31 do display properties typical of a tachykinin, but that peptides with Ile at this position do not.
 ...
PMID:Comparative studies on peptides representing the so-called tachykinin-like region of the Alzheimer Abeta peptide [Abeta(25-35)]. 982 Aug 20

Immunocytochemical techniques was used to compare the proportion of neurons expressing various neurotransmitters (tyrosine hydroxylase, choline acetyltransferase and gamma-aminobutyric acid), neuropeptides (Leu-enkephalin and substance P) and neural cell adhesion molecules (NCAM) in the hippocampus, frontal (area 10) and occipital (area 17) cortices of neurologically normal elderly humans to that of age-matched Alzheimer disease (AD) patients. There was no difference in the proportion of GABAergic and cholinergic cells between the normal and AD groups in all three brain regions studied. However, the catecholaminergic cells in the frontal cortex of the AD patients revealed a significant decrease. The catecholaminergic cells present in the cortex were both neurons and astrocytes, as revealed by a double immunostaining of tyrosine hydroxylase and glial fibrillary acid protein (GFAP). Furthermore, the difference in the proportion of cells expressing Substance P and Leu-enkephalin was minimal between the two groups studied. Although there was little difference in the levels of NCAM in the occipital cortex and hippocampus of the two groups, there were significantly fewer positive NCAM neurons in the frontal cortex of AD than normal aging individuals.
 ...
PMID:Neurotransmitters, peptides, and neural cell adhesion molecules in the cortices of normal elderly humans and Alzheimer patients: a comparison. 1019 33

The three-dimensional structure of beta amyloid peptide (25-35) in aqueous solution with 50% (vol/vol) 2,2,2-trifluoroethanol was determined by NMR spectroscopy. Beta amyloid peptide(Abeta) is the major component of senile plaques found in the brain of patient of Alzheimer's disease. Abeta25-35 is biologically active fragment of Abeta and exhibits some sequence homology with the tachykinin family. In this study, we present the structural similarity between Abeta25-35 and substance P which is a member of tachykinin family in order to examine the possibility of sharing pathways mediated by tachykinin receptors. Both peptides have alpha-helical structures in their C-terminal regions and aromatic rings or hydrophobic side chains in the center of the helix protrude outside. These conformational features are expected to be the key for the interaction with the receptors.
 ...
PMID:Comparison of the structures of beta amyloid peptide (25-35) and substance P in trifluoroethanol/water solution. 1056 86

The present study investigated the neurochemical and behavioural sequelae following chronic intracerebroventricular infusion of beta-amyloid (1-40) in rats. beta-amyloid was either infused intermittently via implanted cannulae on the day of operation and subsequently on postsurgical days 4, 7, 10, and 13 (Experiment 1), or continuously using osmotic pumps for 14 days (Experiment 2). The same amount of beta-amyloid was delivered under both infusion regimes. In both experiments, beta-amyloid infusion led to severe deficits in the acquisition of a spatial reference memory task conducted on postoperative days 10 to 14. The animals were sacrificed on the postoperative day 15 for neurochemical analyses. These included radioenzymatic and radioimmunoassays, designed to determine choline acetyltransferase activity and the contents of neuropeptides (somatostatin, substance P, and neuropeptide Y), respectively. Experiment 2 also included solution-hybridisation-RNAase protection assay for preprosomatostatin mRNA quantification. There was a significant reduction in choline acetyltransferase activity and in the levels of substance P as well as somatostatin and preprosomatostatin mRNA in the cortical mantle of beta-amyloid-treated rats, compared to controls in both experiments. Appreciable reductions in choline acetyltransferase activity and somatostatin level were also apparent in the hippocampus. In contrast, beta-amyloid infusion did not significantly affect the brain level of neuropeptide Y. The present study demonstrated that chronic infusion of beta-amyloid can lead to a reduction in the levels of selected neuropeptides resembling the pattern seen in Alzheimer's disease patients.
 ...
PMID:Reduction in somatostatin and substance P levels and choline acetyltransferase activity in the cortex and hippocampus of the rat after chronic intracerebroventricular infusion of beta-amyloid (1-40). 1058 23

Mice with a genetic disruption of the dopamine transporter (DAT-/-) exhibit locomotor hyperactivity and profound alterations in the homeostasis of the nigrostriatal system, e.g. a dramatic increase in the extracellular dopamine level. Here, we investigated the adaptive changes in dopamine D1, D2 and D3 receptor gene expression in the caudate putamen and nucleus accumbens of DAT-/- mice. We used quantitative in situ hybridization and found that the constitutive hyperdopaminergia results in opposite regulations in the gene expression for the dopamine receptors. In DAT-/- mice, we observed increased mRNA levels encoding the D3 receptor (caudate putamen, +60-85%; nucleus accumbens, +40-107%), and decreased mRNA levels for both D1 (caudate putamen, -34%; nucleus accumbens, -45%) and D2 receptors (caudate putamen, -36%; nucleus accumbens, -33%). Furthermore, we assessed the phenotypical organization of the striatal efferent neurons by using double in situ hybridization. Our results show that in DAT+/+ mice, D1 and D2 receptor mRNAs are segregated in two different main populations corresponding to substance P and preproenkephalin A mRNA-containing neurons, respectively. The phenotype of D1 or D2 mRNA-containing neurons was unchanged in both the caudate putamen and nucleus accumbens of DAT-/- mice. Interestingly, we found an increased density of preproenkephalin A-negative neurons that express the D3 receptor mRNA in the nucleus accumbens (core, +35%; shell, +46%) of DAT-/- mice. Our data further support the critical role for the D3 receptor in the regulation of D1-D2 interactions, an action being restricted to neurons coexpressing D1 and D3 receptors in the nucleus accumbens.
 ...
PMID:Differential regulation of the dopamine D1, D2 and D3 receptor gene expression and changes in the phenotype of the striatal neurons in mice lacking the dopamine transporter. 1065 56

Amyloid beta peptides (Abetas) of 39-43 amino acids constitute the major protein component of the amyloid plaques found in Alzheimer's disease brain. The generation of Abetas is regulated by the phosphoinositide (PI) pathway, which commonly couples to transmitter receptors. This study reports evidence for the activation of the PI pathway by Abetas in Xenopus oocytes expressing rat brain RNA. The naturally occurring peptides Abeta1-40 and Abeta1-42 were both active, whereas the cytotoxic fragment Abeta25-35 and the reverse peptide Abeta40-1 did not stimulate the PI pathway. Abetas rapidly lost potency in solution, suggesting that they were active only in their non-aggregated form. The Abeta response was saturable and not reduced by a substance P antagonist. This pharmacology excludes the participation of known Abeta binding proteins. The results indicate that a PI coupled receptor for non-aggregated Abeta may be present in brain.
 ...
PMID:Amyloid beta peptides activate the phosphoinositide signaling pathway in oocytes expressing rat brain RNA. 1071 21

Amyloid beta peptides (AbetaP) deposit as plaques in vascular and parenchymal areas of Alzheimer's disease (AD) tissues and Down's syndrome patients. Although neuronal toxicity is a feature of late stages of AD, vascular pathology appears to be a feature of all stages of AD. Globular and nonfibrillar AbetaPs are continuously released during normal cellular metabolism, form calcium-permeable channels, and alter cellular calcium level. We used atomic force microscopy, laser confocal microscopy, and calcium imaging to examine the real-time and acute effects of fresh and globular AbetaP(1-42), AbetaP(1-40), and AbetaP(25-35) on cultured endothelial cells. AbetaPs induced morphological changes that were observed within minutes after AbetaP treatment and led to eventual cellular degeneration. Cellular morphological changes were most sensitive to AbetaP(1-42). AbetaP(1-42)-induced morphological changes were observed at nanomolar concentrations and were accompanied by an elevated cellular calcium level. Morphological changes were prevented by anti-AbetaP antibody, AbetaP-channel antagonist zinc, and the removal of extracellular calcium, but not by tachykinin neuropeptide, voltage-sensitive calcium channel blocker cadmium, or antioxidants DTT and Trolox. Thus, nanomolar fresh and globular AbetaP(1-42) induces rapid cellular degeneration by elevating intracellular calcium, most likely via calcium-permeable AbetaP channels and not by its interaction with membrane receptors or by activating oxidative pathways. Such rapid degeneration also suggests that the plaques, and especially fibrillar AbetaPs, may not have a direct causative role in AD pathogenic cascades.
 ...
PMID:Fresh and globular amyloid beta protein (1-42) induces rapid cellular degeneration: evidence for AbetaP channel-mediated cellular toxicity. 1083 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>