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)

Sciatica can be caused by a herniated disc (compressive neuropathy) or by the process of disc degeneration (noncompressive neuropathy). Laminectomy and discectomy usually produce a good result in compressive neuropathy, whereas surgery for noncompressive neuropathy, if necessary, consists of complete excision of the disc and anterior interbody fusion, posterior fusion, or both. Noncompressive spinal radiculitis is a biochemical, not a biomechanical, problem. Phospholipase A2, substance P, and increased fibrinolytic activity have been implicated in the process.
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PMID:Noncompressive spinal radiculitis. 150 20

We have compared several known releasers of endothelium-derived relaxing factor (EDRF)(13) in respect to their potencies to generate EDRF by endothelium of rabbit aortic strips (RbA) superfused with Krebs' buffer. The vasorelaxation by EDRF which is equivalent to 10 pmoles of GTN was evoked by 0.7 pmoles of substance P(SP), 50 pmoles of acetylcholine (Ach), 521 pmoles of calcium ionophore A 23187, 2720 pmoles of ADP. Threshold potencies of these agonists are inversely proportional to the maximum amount of EDRF released. Phospholipase C (PLC) from Clostridium perfringens at a dose of 0.1 U caused the relaxation of a similar magnitude. Phospholipase A2 (1 U), thrombin (1 U), bradykinin (30 nmoles) and serotonin (10 pmoles) did not release EDRF. It is concluded that endothelial cells of RbA differ from endothelial cells of other species in their susceptibility to release EDRF in response to various agonists.
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PMID:Quantification of the potencies of EDRF-releasers from isolated rabbit aortic strips. 166 77

Footpad injection of endotoxin causes exclusive ocular inflammation in the rat. In order to clarify its physiopathologic mechanism, we studied the effect of different treatments on endotoxin-induced uveitis (EIU). Salmonella endotoxin was injected into the footpads of Lewis rats. 18 hr later, inflammation was assessed by evaluating proteins and cells in the anterior chamber; arachidonic acid (AA) metabolites, prostaglandin E2 and leukotriene B4, as well as substance P were measured by radioimmunoassay, and Ia-(MHC class II)-antigen expression in ciliary body was assessed by immunohistochemistry. The effect of inhibitors of phospholipase A2 (EPC), of lipoxygenase (azelastine) and of cyclo-oxygenase (diclofenac), as well as dexamethasone, cyclosporine (CsA) and anti-Ia antibody, were evaluated on these parameters. Phospholipase A2 inhibitor EPC and dexamethasone were most effective on inflammation: they also reduced AA metabolites very effectively and prevented Ia-expression. Lipoxygenase and cyclo-oxygenase inhibitors were partially effective on inflammation and on AA metabolites but failed to prevent Ia-expression. Immunosuppressive treatments (CsA and anti-Ia-antibody) also reduced inflammation. Our findings suggest that inflammation mediators initiate inflammation in EIU. Ia-Ag-expression is secondarily produced by mediators leading to additional inflammation due to immune mediated mechanisms.
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PMID:Immunopharmacological analysis of endotoxin-induced uveitis in the rat. 254 43

Phospholipase A(2) (PLA(2)) forms are expressed in spinal cord, and inhibiting spinal PLA(2) induces a potent antihyperalgesia. Here, we examined the antihyperalgesic effects after systemic and i.t. delivery of four compounds constructed with a common motif consisting of a 2-oxoamide with a hydrocarbon tail and a four-carbon tether. These molecules were characterized for their ability to block group IVA calcium-dependent PLA(2) (cPLA(2)) and group VIA calcium-independent PLA(2) (iPLA(2)) in inhibition assays using human recombinant enzyme. The rank ordering of potency in blocking group IVA cPLA(2) was AX048 (ethyl 4-[(2-oxohexadecanoyl)amino]butanoate), AX006 (4-[(2-oxohexadecanoyl)amino]butanoic acid), and AX057 (tert-butyl 4-[(2-oxohexadecanoyl)amino]butanoate) > AX010 (methyl 4-[(2-oxohexadecanoyl)amino]butanoate) and for inhibiting group VIA iPLA(2) was AX048, AX057 > AX006, and AX010. No agent altered recombinant cyclooxygenase activity. In vivo, i.t. (30 mug) and systemic (0.2-3 mg/kg i.p.) AX048 blocked carrageenan hyperalgesia and after systemic delivery in a model of spinally mediated hyperalgesia induced by i.t. substance P (SP). The other agents were without activity. In rats prepared with lumbar i.t. loop dialysis catheters, SP evoked spinal prostaglandin E(2) (PGE(2)) release. AX048 alone inhibited PGE(2) release. Intrathecal SR141617, a cannabinoid CB1 inhibitor at doses that blocked the effects of i.t. anandamide had no effect upon i.t. AX048. These results suggest that AX048 is the first systemically bioavailable compound with a significant affinity for group IVA cPLA(2), which produces a potent antihyperalgesia. The other agents, although demonstrating enzymatic activity in cell-free assays, appear unable to gain access to the intracellular PLA(2) toward which their action is targeted.
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PMID:Systemic and intrathecal effects of a novel series of phospholipase A2 inhibitors on hyperalgesia and spinal prostaglandin E2 release. 1620 28