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 serpin-enzyme complex (SEC) receptor mediates catabolism of alpha 1-antitrypsin (alpha 1-AT)-elastase complexes and increases in synthesis of alpha 1-AT in cell culture. The SEC receptor recognizes a pentapeptide domain on alpha 1-AT-elastase complexes (alpha 1-AT 370-374), and the same domain in several other serpins, amyloid-beta peptide, substance P, and other tachykinins. Thus, it has also been implicated in the biological properties of these ligands, including the neurotoxic effect of amyloid-beta peptide. In this study, we examined the possibility that the SEC receptor mediates the previously described neutrophil chemotactic activity of alpha 1-AT-elastase complexes, and whether the other ligands for the SEC receptor have neutrophil chemotactic activity. The results show that 125I-peptide 105Y (based on alpha 1-AT 359-374) binds specifically and saturably to human neutrophils, and the characteristics of this binding are almost identical to that of monocytes and hepatoma-derived hepatocytes. Peptide 105Y and amyloid-beta peptide mediate chemotaxis for neutrophils with maximal stimulation at 1-10 nM. Mutant or deleted forms of peptide 105Y, which do not bind to the SEC receptor, have no effect. The neutrophil chemotactic effect of alpha 1-AT-elastase complexes is blocked by antiserum to peptide 105Y and by antiserum to the SEC receptor, but not by control antiserum. Preincubation of neutrophils with peptide 105Y or substance P completely blocks the chemotactic activity of amyloid-beta peptide, but not that of FMLP. These results, therefore, indicate that the SEC receptor can be modulated by homologous desensitization and raise the possibility that pharmacological manipulation of this receptor will modify the local tissue response to inflammation/injury and the neuropathologic reaction of Alzheimer's disease.
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PMID:The serpin-enzyme complex (SEC) receptor mediates the neutrophil chemotactic effect of alpha-1 antitrypsin-elastase complexes and amyloid-beta peptide. 132 93

The conditioned corral preference paradigm was used to assess reinforcing effects of substance P (SP) and its N- and C-terminal fragments injected unilaterally into the region of the nucleus basalis magnocellularis (NBM) in rats. Behavioral testing was carried out in a circular open field, consisting of 4 quadrants equally preferred by the animals prior to conditioning. A single conditioning trial was performed. Rats received one microinjection (0.5 microliter) of SP (0.74 pmol), of the N-terminal fragment SP (1-7) and the C-terminal fragment analog DiMe-C7 (each at doses of 0.074, 0.74, and 74 pmol), or vehicle (phosphate-buffered saline; PBS). After injection the rats were placed into the open field with the four quadrants being separated by Plexiglas barriers (closed corral). During the test for conditioned corral preference, when provided a choice between the four quadrants, only those rats injected with SP and the equimolar dose of DiMe-C7 (0.74 pmol) spent more time in the treatment corral, indicative of a positively reinforcing action. None of the other doses of DiMe-C7 and of SP(1-7) influenced the preference behavior. For rats injected with 0.74 pmol SP, SP (1-7), and DiMe-C7, a behavioral analysis was performed for the 15 min conditioning trial. SP and DiMe-C7 reduced rearing and grooming behavior, whereas DiMe-C7 and SP(1-7) increased locomotor activity. However, the acute behavioral effects of SP and its fragments were not correlated with the subsequent place preference behavior during the test trial. The results are discussed in the framework of a structure/activity relationship for the positively reinforcing properties of SP in the region of the NBM. Furthermore, neuropathological implications of the present data are considered, since the homologous nucleus basalis of Meynert in man is known to degenerate in Alzheimer's disease, which is characterized behaviorally by a progressive deterioration in associative functioning.
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PMID:Positively reinforcing effects of the neurokinin substance P in the basal forebrain: mediation by its C-terminal sequence. 137 Sep 40

Amyloid deposits are characteristic of Alzheimer's Disease (AD) and there is growing evidence that amyloid may play an important role in the genesis of this neurodegenerative disease. This review discusses data which suggests that reactive astrocytes and microglia may be a necessary concomitant with amyloid to produce the neuropathology which manifests as AD. Several hypotheses and supporting data for mechanisms by which reactive astrocytes may mediate this neuropathology are presented. These include the possibility that amyloid induces excitotoxicity by interferring with astrocytic glutamate uptake, the possibility that amyloid has this effect via an action on a tachykinin-related receptor and the possibility that proteoglycans released by astrocytes may facilitate the deposition of amyloid plaques. Both symptomatic treatment to enhance cognitive function and treatment to stop the progression of AD are needed. It is hoped that answers to some of the unique questions raised here may provide new insight into the etiology and treatment of AD.
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PMID:Astroglia in Alzheimer's disease. 152 41

The incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) among the Chamorros in Guam is remarkably high. The patients with ALS have clinical and pathological characteristics similar to those in other parts of the world. The PDC patients display parkinsonism and progressive dementia and show a characteristic neuronal loss in certain parts of the central nervous system such as the hippocampus and substantia nigra. The Guamanian patients with ALS and PDC commonly have widespread Alzheimer's neurofibrillary changes, but without the associated senile plaques. We have applied immunohistochemical procedures to examine the expression of marker substances in Guamanian ALS and PDC. The markers studied include tau protein, ubiquitin, beta proteins, synaptophysin, calcineurin, Met-enkephalin, substance P and tyrosine hydroxylase. The results were compared with the findings in patients with Alzheimer's disease, Parkinson's disease, sporadic ALS and familial ALS.
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PMID:Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies. 158 17

The salient pathological feature of Alzheimer disease (AD) is the presence of a high density of amyloid plaques in the brain tissue of victims. The plaques are predominantly composed of human beta-amyloid peptide (beta A4), a 40-mer whose neurotoxicity is related to its aggregation. Radioiodinated human beta A4 is rapidly deposited in vitro from a dilute (less than 10 pM) solution onto neuritic and diffuse plaques and cerebrovascular amyloid in AD brain tissue, whereas no deposition is detectable in tissue without performed plaques. This growth of plaques by deposition of radiolabeled beta A4 to plaques is reversible, with a dissociation half-time of approximately 1 h. The fraction of grey matter occupied by plaques that bind radiolabeled beta A4 in vitro is dramatically larger in AD cortex (23 +/- 11%) than in age-matched normal controls (less than 2%). In contrast to the human peptide, rat/mouse beta A4 (differing at three positions from human beta A4) does not affect the deposition of radiolabeled human beta A4. beta A4 has no detectable interaction with tachykinin receptors in rat or human brain. The use of radioiodinated beta A4 provides an in vitro system for the quantitative evaluation of agents or conditions that may inhibit or enhance the growth or dissolution of AD plaques. This reagent also provides an extremely sensitive method for visualizing various types of amyloid deposits and a means for characterizing and locating sites of amyloid peptide binding to cells and tissues.
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PMID:Reversible in vitro growth of Alzheimer disease beta-amyloid plaques by deposition of labeled amyloid peptide. 160 56

The amyloid beta protein (ABP) has been shown to interact with the substance P (SP) receptor in a cell culture model that may mimic the pathogenesis of Alzheimer's disease. In the present study, however, 4 fragments of ABP (beta 1-42, beta 1-16, beta 17-28, and beta 25-35) failed to interact with SP-induced Ca2+ mobilization in SP receptor-expressing cultured cells. Therefore, the action of these ABP-related peptides in our cultured cells is unrelated to the SP receptor.
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PMID:Amyloid beta protein substituent peptides do not interact with the substance P receptor expressed in cultured cells. 166 16

Extensive evidence indicates that disruption of cholinergic function is characteristic of aging and Alzheimer's disease (AD), and experimental manipulation of the cholinergic system in laboratory animals suggests age-related cholinergic dysfunction may play an important role in cognitive deterioration associated with aging and AD. Recent research, however, suggests that cholinergic dysfunction does not provide a complete account of age-related cognitive deficits and that age-related changes in cholinergic function typically occur within the context of changes in several other neuromodulatory systems. Evidence reviewed in this paper suggests that interactions between the cholinergic system and several of these neurotransmitters and neuromodulators--including norepinephrine, dopamine, serotonin, GABA, opioid peptides, galanin, substance P, and angiotensin II--may be important in learning and memory. Thus, it is important to consider not only the independent contributions of age-related changes in neuromodulatory systems to cognitive decline, but also the contribution of interactions between these systems to the learning and memory deficits associated with aging and AD.
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PMID:The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory. 167 82

Substance P-like immunoreactivity was visualized by immunohistochemical methods in 20 postmortem brains: 6 senile, 4 presenile Alzheimer dementia (AD), 3 AD with interhemispheric asymmetric cortical atrophy, and 7 control cases. For all pathological cases, the SP-like immunoreactivity was significantly reduced in the neocortical areas and in the hippocampus. This contrasted with an enhanced SP-like immunoreactivity in the pallidum and the substantia nigra in AD brains and a more pronounced SP-like immunoreactivity in the more atrophic side in the asymmetrically atrophied brains.
Alzheimer Dis Assoc Disord 1990
PMID:Substance P immunoreactivity in Alzheimer disease: a study in cases presenting symmetric or asymmetric cortical atrophy. 169 May 54

A comparative topographical immunohistochemical analysis was performed on the basal ganglia (including the substantia nigra) in Guamanian parkinsonism-dementia complex, idiopathic Parkinson's disease (PD), and Alzheimer's disease (AD). The striatal projection neurons and their efferent fibers were examined by using antibodies to calcineurin, methionine-enkephalin, and substance P. Tyrosine hydroxylase served as a marker for nigrostriatal dopaminergic neurons. The basal ganglia of patients with parkinsonism-dementia complex reacted strongly with all of the antibodies and the reaction products exhibited a normal distribution pattern. These findings suggest that the striatal output system is well preserved in patients with this disease. Similar results were obtained in patients with AD or PD. However, as compared to the patients with AD or PD, patients with parkinsonism-dementia complex showed severe reduction (greater than 90%) in the number of dopaminergic neurons in both the lateral and the medial portions of the substantia nigra. In view of the functional cortico-subcortical loops, these findings could explain the parkinsonian features and in part the cognitive impairment that occur in parkinsonism-dementia complex on Guam.
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PMID:Immunohistochemical study of the striatal efferents and nigral dopaminergic neurons in parkinsonism-dementia complex on Guam in comparison with those in Parkinson's and Alzheimer's diseases. 169 18

Substance P-like immunoreactivity, choline acetyltransferase (ChAT) activity and muscarinic cholinergic receptors were measured in brains from 9 individuals with senile dementia of the Alzheimer type (AD), 4 individuals with multi-infarct dementia (MID), 6 individuals with mixed type of dementia (AD/MID) and 9 controls. The ChAT activity was markedly reduced (50-60%) in the hippocampus of all demented brains. The number of muscarinic cholinergic receptors was reduced only in the MID and AD/MID brains. No significant difference in substance P-like immunoreactivity was measured in 4 regions of AD brains in comparison to controls. In the combined MID plus AD/MID groups a significant reduction in substance P-like immunoreactivity (-35%) was measured in the hippocampus while no change was found in the frontal cortex, amygdala and caudate nucleus. The findings support the assumption of differences in selectivity of damage between AD and AD/MID, MID.
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PMID:Substance P-like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in Alzheimer's disease and multi-infarct dementia. 169 12


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