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)

Endotoxin-induced uveitis (EIU) can be produced by systemic injection of endotoxin (ET). It is not clear yet why exclusive ocular involvement occurs in this model. To clarify this question and to establish the sequence of inflammatory events, EIU was induced in Lewis rats by footpad injection of Salmonella ET. Ocular inflammatory response (anterior chamber cells and proteins), aqueous inflammation mediators (thromboxane B2, prostaglandin E2, leukotriene B4 and substance P) and MHC class 2 (Ia) antigen expression in the ciliary body were monitored for 72 hours. Thromboxane B2 was detected early in the aqueous humor, peaking already 1 hour after ET injection. Prostaglandin E2 & leukotriene B4 peaks and a second peak of thromboxane B2 were recorded 18 hours after ET-injection, at the time of maximal ocular inflammation. MHC-class 2 expression was first detected in the ciliary body stroma at the vascular level 6 hours after ET injection and was massively expressed in the ciliary body epithelium at 18 and 72 hours. It is hypothesized that ciliary body endothelium is particularly sensitive to the effect of ET and is the site of thrombocyte adherence. Vascular damage leads in succession to cellular infiltration, release of inflammation mediators and disruption of blood-ocular barrier. MHC-class 2 expression is a secondary phenomenon and is probably at the origin of additional tissue damage from immune effector mechanisms.
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PMID:Endotoxin-induced uveitis (EIU) in the rat: a study of inflammatory and immunological mechanisms. 169 Nov 57

Cells of the immune system synthesize prolactin and express mRNA and receptors for that hormone. Interleukin 1, interleukin 6, gamma interferon, tumor necrosis factor, platelet activator factor, and substance P participate in the release of prolactin. This hormone is involved in the pathogenesis of adjuvant arthritis and restores immunocompetence in experimental models. In vitro studies suggest that lymphocytes are an important target tissue for circulating prolactin. Prolactin antibodies inhibit lymphocyte proliferation. Prolactin is comitogenic with concanavalin A and induces interleukin 2 receptors on the surface of lymphocytes. Prolactin stimulates ornithine decarboxylase and activates protein kinase C, which are pivotal enzymes in the differentiation, proliferation, and function of lymphocytes. Cyclosporine A interferes with prolactin binding to its receptors on lymphocytes. Hyperprolactinemia has been found in patients with systemic lupus erythematosus. Fibromyalgia, rheumatoid arthritis, and low back pain patients present a hyperprolactinemic response to thyrotropin-releasing hormone. Experimental autoimmune uveitis, as well as patients with uveitis whether or not associated with spondyloarthropathies, and patients with psoriatic arthritis may respond to bromocriptine treatment. Suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine A with significantly less toxicity. Prolactin may also be a new marker of rejection in heart-transplant patients. This body of evidence may have an impact in the study of rheumatic disorders, especially connective tissue diseases. A role for prolactin in autoimmune diseases remains to be demonstrated.
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PMID:Prolactin, immunoregulation, and autoimmune diseases. 206 74

Intraocular inflammation was induced in the rat by footpad injection of salmonella endotoxin in order to study the influence of chemical inflammation mediators in this uveitis model. Ocular inflammation was assessed 1, 6, 18, 24 and 72 h after endotoxin administration as well as in control rats, by measuring aqueous protein concentration, aqueous inflammatory cell content, and pupillary diameter. Thromboxane B2 (TXB2), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2-alpha), leukotriene B4 (LTB4), and substance P were simultaneously measured in the aqueous humor by radioimmunoassay. Inflammation parameters peaked at 18 h. TXB2 was already significantly elevated at 1 h. PGE2 peak values of 2.7 ng/ml were reached at 18 h. PGF2-alpha was never significantly raised over control values. LTB4 peaked at 18 h, together with a polymorphonuclear peak. Substance P was significantly elevated after 6 h. It is concluded that maximal uveitis in this model occurs at 18 h. TXB2 is an early mediator, and PGE2 is probably implicated in blood-ocular barrier disruption for which levels as high as 2.7 ng/ml in aqueous seem necessary. PGF2-alpha does not play a major role in this model, while LTB4 seems to be the main chemotactic factor for polymorphonuclears (PMNs) in the anterior chamber and substance P is clearly related to pupil miosis.
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PMID:Endotoxin-induced uveitis in the rat. A study of the role of inflammation mediators. 246 14

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

The role of nerve conduction was studied in acute experimental uveitis caused by antidromic trigeminal nerve stimulation, prostaglandin E1 and E2 (PGE1 and PGE2), capsaicin and substance P (SP). Systemic indomethacin was used to prevent formation of endogenous prostaglandins, and intracameral injection of tetrodotoxin (TTX) was used to block nerve conduction. 10 micrograms TTX prevented the miosis and reduced the rise in intraocular pressure (IOP) usually caused by antidromic trigeminal nerve stimulation. At a low dose of PGE1 the IOP rise was blocked by TTX. At higher doses of PGE1 and PGE2 the pressure effect was not blocked by TTX; the miotic effect was markedly diminished. Capsaicin caused a rise in IOP that was almost totally blocked by TTX, while the miosis at high doses seemed unaffected. At low doses, capsaicin-induced miosis could be abolished by TTX. SP caused miosis in TTX treated eyes similar to that in untreated eyes; the IOP rise was delayed by TTX. The results indicate that nerve conduction plays a role in the IOP reaction caused by low doses of PGE1 and by capsaicin and SP. The mechanism suggested is an axon reflex, elicited in the anterior uvea and resulting in transmitter release in the ciliary processes. Nerve conduction with release of SP or a similar substance in the iris seems to be required for the miotic effects of PGE1 and PGE2. SP and capsaicin are similar in not requiring nerve conduction to cause miosis, but the capsaicin effect probably requires presence of nerves, since denervated eyes--which respond to SP--have been reported no to respond to capsaicin does similar to those used here.
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PMID:Ocular responses to antidromic trigeminal stimulation, intracameral prostaglandin E1 and E2, capsaicin and substance P. 617 Feb 10