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)

Human beta-endorphin-like immunoreactive substances (beta h-EI) in human cerebrospinal fluid (CSF) were determined radioimmunologically. The cross reactivity of the antibodies to human beta-endorphin (beta h-E) amounted to 40% for human beta-lipotropin (beta h-LPH) whilst it was less than 1% for leu- and metenkephalin, alpha- and gamma-endorphin, fraction I and II [5], substance P and alpha-MSH. Prior to radioimmunological determination, an adsorbtion of beta h-EI from CSF with silicic acid was carried out and followed by a desorbtion, using a mixture of aceton/hydrochloric acid. This method was chosen because of the ratio of beta h-LPH to beta h-E in the desorbate can be shifted in favour of beta h-E owing to the variation in recoveries r (r beta h-LPH = 33%, r beta h-E = 64%). On the one hand, this enables a more specific determination of beta h-E and, on the other hand, and separation of any peptidase than may be present [9]. An adsorbtion/desorbtion of 2 ml CSF surfaces to prove the presence of 20-150 pg/ml (65-48 fmol/ml) of beta h-EI. The CSF of 28 patients with various neurological diseases was examined and 24 of them had concentrations of 20-70 pg/ml beta h-EI. The remaining four which had concentrations less than 20 pg/ml, came from meningitis patients undergoing corticoid therapy. A purchasable RIA kid was tested for its determination of beta h-E and was found to be unsuitable.
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PMID:A simplified radioimmunological method for the determination of human beta-endorphin in cerebrospinal fluid. 616 16

The present study investigated whether the endogenous vasodilating neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) contribute to pial arteriolar vasodilatation in the early phase of pneumococcal meningitis in the rat. Using a closed cranial window preparation we measured the diameters of pial arterioles during 4 h after pneumococcal infection. Arteriolar vasodilatation in infected rats was significantly attenuated by pretreatment with the SP-antagonist spantide up to 3 h after infection. Neither post-treatment with spantide (administered 2 h after infection) nor pretreatment with the CGRP antagonist CGRP(8-37) affected the pneumococci-induced pial arteriolar dilatation. These data suggest that SP is involved as a mediator in early pneumococci-induced dilatation of pial arterioles.
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PMID:Involvement of substance P in pial arteriolar vasodilatation during pneumococcal meningitis in the rat. 754 53

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

Severe headache and meningism provide clear evidence for the activation of trigeminal neurotransmission in meningitis. The authors assessed the antiinflammatory potential of 5HT1B/D/F receptor agonists (triptans), which inhibit the release of proinflammatory neuropeptides from perivascular nerve fibers. In a 6-hour rat model of pneumococcal meningitis, zolmitriptan and naratriptan reduced the influx of leukocytes into the cerebrospinal fluid, and attenuated the increase of regional cerebral blood flow. Elevated intracranial pressure as well as the brain water content at 6 hours was reduced by triptans. These effects were partially reversed by a specific 5HT1D as well as by a specific 5HT1B receptor antagonist. Meningitis caused a depletion of calcitonin gene-related peptide (CGRP) and substance P from meningeal nerve fibers, which was prevented by zolmitriptan and naratriptan. In line with these findings, patients with bacterial meningitis had significantly elevated CGRP levels in the cerebrospinal fluid. In a mouse model of pneumococcal meningitis, survival and clinical score at 24 hours were significantly improved by triptan treatment. The findings suggest that, besides mediating meningeal nociception, meningeal nerve fibers contribute to the inflammatory cascade in the early phase of bacterial meningitis. Adjunctive treatment with triptans may open a new therapeutic approach in the acute phase of bacterial meningitis.
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PMID:Triptans reduce the inflammatory response in bacterial meningitis. 1217 84

There is increasing evidence that the tachykinin substance P (SP) can augment inflammatory immune responses within the CNS. We have recently demonstrated that resident CNS cells express high-affinity receptors for this neuropeptide (neurokinin-1 receptors [NK-1R]), and we have shown that SP can significantly augment glial inflammatory responses to clinically relevant Gram-negative bacteria. Furthermore, we provided evidence that endogenous SP/NK-1R interactions are an essential component in the initiation and/or progression of CNS inflammation following in vivo exposure to these pathogens. In this study, we demonstrate that SP similarly enhances inflammatory glial responses to the major Gram-positive causative agent of bacterial meningitis, Streptococcus pneumoniae, and show that endogenous SP/NK-1R interactions play a critical role in the development of CNS inflammation in an in vivo model of pneumococcal meningitis. Importantly, we provide the first demonstration, to our knowledge, that pharmacological targeting of the NK-1R not only prevents the development of damaging inflammation when administered prophylactically, but can also limit or reverse neuroinflammation associated with an established streptococcal CNS infection when delivered therapeutically. We show that an NK-1R antagonist attenuates increases in CNS inflammatory cytokine levels and decreases in immunosuppressive cytokine production associated with an ongoing S. pneumoniae infection. Furthermore, we demonstrate that such a therapeutic intervention reverses infection-associated gliosis and demyelination in the absence of changes in CNS bacterial burden. Together, these results suggest that targeting SP/NK-1R interactions is a strategy worthy of further study for the treatment of microbially induced neuroinflammation.
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PMID:Prophylactic and therapeutic targeting of the neurokinin-1 receptor limits neuroinflammation in a murine model of pneumococcal meningitis. 2156 62

Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis.
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PMID:Blocking neurogenic inflammation for the treatment of acute disorders of the central nervous system. 2381 99

The inflammatory responses of resident central nervous system (CNS) cells are now known to play a critical role in the initiation and progression of an array of infectious and sterile neuroinflammatory disorders such as meningitis, encephalitis, Parkinson's disease, Alzheimer's disease and multiple sclerosis (MS). Regulating glial inflammatory responses in a timely manner is therefore critical in preserving normal CNS functions. The neuropeptide substance P is produced at high levels within the CNS and its selective receptor, the neurokinin 1 receptor (NK-1R), is abundantly expressed by neurons and is present on glial cell types including microglia and astrocytes. In addition to its functions as a neurotransmitter in the perception of pain and its essential role in gut motility, this tachykinin is widely recognized to exacerbate inflammation at peripheral sites including the skin, gastrointestinal tract and the lungs. Recently, a number of studies have identified a role for substance P and NK-1R interactions in neuroinflammation and described the ability of this neuropeptide to alter the immune functions of activated microglia and astrocytes. In this review article, we describe the expression of substance P and its receptor by resident CNS cells, and we discuss the ability of this neuropeptide to exacerbate the inflammatory responses of glia and immune cells that are recruited to the brain during neurodegenerative diseases. In addition, we discuss the available data indicating that the NK-1R-mediated augmentation of such responses appears to be detrimental during microbial infection and some sterile neurodegenerative disorders, and propose the repurposed use of NK-1R antagonists, of a type that are currently approved as anti-emetic and anti-anxiolytic agents, as an adjunct therapy to ameliorate the inflammatory CNS damage in these conditions.
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PMID:The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders. 2810 Oct 5