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)

There is increasing evidence that local substance P (SP) exacerbates peripheral inflammations, partly by stimulating production of inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). SP may play similar roles in certain central nervous system inflammations. Multiple sclerosis plaques, for example, form around veins which are innervated by unmyelinated SP-containing fibers, and astrocytes in multiple sclerosis plaques stain for SP. We tested whether SP could stimulate IL-1 and TNF alpha production by cultured astrocytes and whether calcium was the second messenger in this process. We found that both SP and the calcium ionophore A23187 raised intracellular calcium ([Ca2+]i) and stimulated IL-1 production in astrocytes. SP also nonsignificantly increased TNF alpha production by astrocytes. Treatment with dibromo BAPTA/AM, an intracellular calcium buffer, blocked SP-induced IL-1 production. These findings indicate that SP induces IL-1 production by astrocytes and uses calcium as a second messenger. Our results indicate local SP may play a role in multiple sclerosis and certain other central nervous system inflammations.
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PMID:Substance P stimulates IL-1 production by astrocytes via intracellular calcium. 128 56

It is a common clinical observation that stretch reflex excitability increases progressively after spinal transsection in man, and causes many severe complications. The purpose of the present study was to investigate the role and mechanism of substance P (SP) on the spinal reflex following spinal cord transsection. We first observed the changes of spontaneous electromyography (EMG) recorded in the paralyzed limbs of spinally transsected rats, and found that the EMG amplitude increased progressively within 40 days. The results were as follows: 1) Spontaneous EMG increased significantly following intrathecal injection of 1 microgram capsaicin, and the sensitivity of EMG to capsaicin increased progressively with time. But this effect could be partly blocked by pretreatment with SP antiserum. 2) Spontaneous EMG increased significantly following intrathecal injection of SP. Yet the time course was relatively short and the amplitude of EMG was lower. These results indicate that SP in the spinal dorsal horn participates in the regulation of myotension, and it is suggested that to decrease SP content in the spinal dorsal horn or block the afferent fibers of dorsal roots might be an effective therapy to reduce the hypermyotension caused by spinal cord injury, multiple sclerosis or other reasons.
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PMID:[The role of substance P in the modulation of myotension in paralyzed limbs after spinal transsection on rats]. 128 59

Multiple sclerosis is an inflammatory disease which affects the white matter of the central nervous system (CNS). The aetiology of this condition is unknown but it is generally believed to represent an autoimmunological response to a component of myelin triggered by an environmental factor, in a genetically susceptible individual. The natural history of the disease, in terms of clinical disability, is unpredictable, and the factors responsible unknown. Substance P is an undecapeptide that acts as a neurotransmitter in the CNS and as a regulator of immune responses. The recent discovery of substance P immunoreactive astrocytes in multiple sclerosis plaques raises the possibility that this peptide may be important both in the development of plaques and in governing the natural history of the disease.
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PMID:Substance P and multiple sclerosis. 137 93

The effect of Semliki Forest Virus, a known central demyelinating agent and a proposed model for multiple sclerosis, on the innervation of the mouse urinary bladder has been examined 3, 6, 9 and 12 weeks after inoculation. Three weeks after Semliki Forest Virus inoculation, vasoactive intestinal polypeptide content of the bladder was reduced and the density of vasoactive intestinal polypeptide-immunoreactive nerves was decreased in the smooth muscle, but not in the mucosa. Choline acetyltransferase activity and neuropeptide Y and substance P content was normal, as was the pattern of innervation by acetylcholinesterase-containing and neuropeptide Y- and substance P-immunoreactive nerve fibres. Six weeks after Semliki Forest Virus inoculation, the choline acetyltransferase activity was significantly reduced. Between 6 and 9 weeks the level of vasoactive intestinal polypeptide in the bladder of Semliki Forest Virus-infected mice significantly increased, so that at 9 weeks it was higher than the control value. However, by 12 weeks both choline acetyltransferase activity and vasoactive intestinal polypeptide content were normal. At this time, the substantial age-related increase in substance P content of the bladder was more pronounced in the Semliki Forest Virus-treated animals. Thus there are transitory changes in the innervation of the mouse bladder by vasoactive intestinal polypeptide-containing and cholinergic nerve fibres after exposure to a central demyelinating agent which may reflect changes in bladder dysfunction seen in multiple sclerosis patients.
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PMID:Neuropeptide immunoreactivity and choline acetyltransferase activity in the mouse urinary bladder following inoculation with Semliki Forest Virus. 170 31

Substance P-like and somatostatin-like immunoreactivities (SPLI and SLI) were determined in ventricular fluid of patients with chronic pain syndromes and in a comparison group with multiple sclerosis, essential tremor, epilepsy and postanoxic myoclonus. Concentrations of SPLI and SLI were non-significantly decreased by 40% and 33% in chronic pain patients as compared with control patients without pain. There were no differences apparent between subgroups of pain patients (deafferentation pain, neoplasia-induced pain, thalamic pain). High pressure liquid chromatography combined with radioimmunoassay showed marked heterogeneity of SPLI and SLI.
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PMID:Substance P-like immunoreactivity and somatostatin-like immunoreactivity in the ventricular fluid of patients with chronic pain syndromes. 183 80

Spinal cord axons and terminals stained for tyrosine hydroxylase-, serotonin- and substance P-like immunoreactivity were examined in guinea-pigs in the paraplegic phase of acute experimental allergic encephalomyelitis, an animal disease model for multiple sclerosis. Fibers positive for monoamine and substance P-like staining that terminated in the lumbar ventral horn appeared to be markedly damaged during the disease. However, no changes were detected in those substance P-containing fibers that terminated in the dorsal horn. It was concluded that small diameter, thinly myelinated or unmyelinated axons that course for long distances in the spinal cord, and, therefore, have a high probability for encountering inflammatory foci, are particularly vulnerable to damage during experimental allergic encephalomyelitis. Damage to these monoaminergic and peptidergic fibers may contribute to the neurological deficits that are associated with this autoimmune nervous system disease.
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PMID:Intraspinal nerve terminals immunoreactive for tyrosine hydroxylase, serotonin and substance P in guinea-pigs with acute experimental allergic encephalomyelitis. 245 45

Substance P (SP)-like immunoreactive cells were identified in postmortem white matter tissue from patients with multiple sclerosis (MS). Labelled cells, which by morphologic criteria could be identified as astrocytes, were located at the edge of both active (e.g. inflammatory) and inactive (e.g. non-inflammatory) MS lesions. By contrast, SP-immunoreactive astrocytes were not found in normal controls and were only occasionally present in other conditions associated with astrogliosis. These data suggest that SP, a potent mediator of vasodilatation and local immune responses, may play a role in the genesis of the MS plaque. These results also extend the repertoire of potential interactions which may occur between astrocytes and cells of the immune system.
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PMID:Substance P immunoreactive astrocytes are present in multiple sclerosis plaques. 248 Aug 34

Substance P (SP) is a central and peripheral neurotransmitter which has been found in multiple sclerosis plaques. SP stimulates peripheral immune cells and may play a role in some chronic inflammatory diseases. Human peripheral monocyte/macrophages have been shown to produce the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) in response to SP. Therefore, in this study we examined rat brain microglia for the presence of SP receptors and production of IL-1 and TNF alpha in response to SP. Microglia had 4900 +/- 950 (mean +/- SE) receptors per cell fitting a two-site model. Four percent of these were high-affinity receptors with a Kd of 8.2 x 10(-8) M +/- 3.6 x 10(-8) M (mean +/- SE), and 96% of them were low-affinity receptors with a Kd of 2.1 x 10(-6) M +/- 5.2 x 10(-7) M (mean +/- SE). Competitive studies with CP 96,345 and other SP analogs demonstrate these to be non-classical NK-1 receptors. SP alone did not stimulate IL-1 or TNF alpha production. However, SP in synergy with lipopolysaccharide (LPS) quadrupled IL-1 production compared to LPS alone, but did not affect TNF alpha production. These results have implications for certain inflammatory conditions in the central nervous system.
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PMID:Production of interleukin-1 by microglia in response to substance P: role for a non-classical NK-1 receptor. 767 97

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.
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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

Neuropeptide Y, cholecystokinin (tetra- and octasulphated peptides) and substance P were measured in lumbar cerebrospinal fluid obtained from patients with various neurologic disorders such as Parkinson's disease, cerebrovascular disorders, multiple sclerosis, tuberculous meningitis and aseptic meningitis. These results are statistically compared with healthy results. The results accumulated showed that the data collected can provide the vital information necessary for designing drug therapy.
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PMID:Variation in cerebrospinal fluid levels of neuropeptide Y, cholecystokinin and substance P in patients with neurological disorders. 1145 34


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