Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02027 (Tranilast)
 205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of OKY-046, a newly synthetized thromboxane A2 (TxA2) synthetase inhibitor, on IgE mediated experimental asthma in guinea pigs was investigated. Indomethacin, a cyclooxygenase inhibitor, and tranilast (N-5'), a potent anti-allergic agent, were used as comparative drugs. OKY-046 clearly improved asthmatic respiratory disorders in guinea pigs. Whereas indomethacin had no effect on the changes of asthmatic respiration, tranilast significantly inhibited the changes. OKY-046 inhibited the in vitro antigen-induced contraction of sensitized guinea pig lung parenchyma. This antigen-induced contraction was also inhibited by tranilast, but not by indomethacin. OKY-046 inhibited the contractions of lung parenchyma caused by leukotriene C4, D4 and E4 (LTC4, LTD4 and LTE4), but not by histamine. Indomethacin showed a biphasic action on the contractile responses caused by histamine and LTD4 Consequently, contractions due to either agonist at low concentrations were inhibited by indomethacin, but those at high concentrations were enhanced. Tranilast inhibited the contraction of lung parenchyma induced by a low concentration of LTD4 but not that produced by histamine. Moreover, OKY-046 inhibited an elevation of concentration of thromboxane B2 (TxB2) in guinea pig lung perfusate after infusion of LTC4 but did not affect the elevation of 6-keto-PGF1 alpha. OKY-046 had no effect on the antigen-induced release of histamine but it inhibited the release of the slow reacting substance of anaphylaxis (SRS-A) from sensitized chopped lung tissues. Indomethacin at a high concentration inhibited the release of histamine but did not affect the release of SRS-A. Tranilast clearly inhibited the release of both mediators. These results suggest that OKY-046 inhibits IgE mediated experimental asthma in guinea pigs and that its main mechanism is related to the inhibition of LT induced contraction of airway smooth muscle and the release of SRS-A from lung tissues.
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PMID:Effect of OKY-046, a new thromboxane A2 synthetase inhibitor, on experimental asthma in guinea pigs. 244 93

The effect of Tranilast [N-(3,4-dimethoxycinnamoyl) anthranilic acid] on the synthesis of prostaglandin D2 (PGD2) by homogenates of rat peritoneal mast cells was investigated. The major cyclooxygenase product formed by mast cell homogenates was PGD2, smaller quantities of PGE2 and PGF2 alpha were also formed. Tranilast suppressed the production of PGD2 in a dose-dependent manner with an IC50 of 0.1 mM. This suppression was due to inhibition of PGD synthetase, but not cyclooxygenase, since the formation of PGE2 and PGF2 alpha were unchanged at a 0.1 mM concentration. In addition, the glutathione-dependent conversion of [14C]PGH2 to PGD2 by PGD synthetase (PGH-D isomerase, EC 5.3.99.2) was inhibited by Tranilast, with 50% inhibition achieved at 0.08 mM in broken cell preparations of rat peritoneal mast cells. Tranilast also inhibited purified rat spleen and brain PGD synthetases. Furthermore, Tranilast prevented the PGD2 generation from intact mast cells stimulated by the calcium ionophore A23187. These results suggest that Tranilast exerts some of its therapeutic effects by prevention of PGD2 generation in mast cells and some other tissues.
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PMID:Inhibitory effect of tranilast on prostaglandin D synthetase. 247 13

We investigated the effects of tranilast on inducible cyclooxygenase (COX2)-mediated prostaglandin E2 (PGE2) production and enzyme induction in interleukin-lbeta (IL-1beta)-stimulated cultured dermal fibroblasts. IL-1beta enhanced PGE2 production in cultured fibroblasts. Tranilast did not affect constitutive cyclooxygenase (COX1) or COX2 activity in non-stimulated or IL-lbeta-stimulated fibroblasts. However, the COX2 expression induced by IL-1beta was inhibited by tranilast. This result, that IL-1beta-induced COX2 expression was suppressed by tranilast, was confirmed by immunohistochemical analysis. Thus, it is possible for tranilast to regulate PGE2 production by inhibiting COX2 induction.
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PMID:Suppressive effects of tranilast on the expression of inducible cyclooxygenase (COX2) in interleukin-1beta-stimulated fibroblasts. 925 70

Tranilast (SB 252218) is a compound initially identified as an anti-atopic agent. Recently the compound has demonstrated clear beneficial effects in animal models of restenosis. Here we confirm tranilast has broad and profound effects on human monocytes, which could contribute to the vascular antifibrotic activity. Tranilast exhibited significant immunomodulatory activity inhibiting endotoxin-induced prostaglandin E(2) (PGE(2); IC(50) = approximately 1-20 microM), thromboxane B(2) (IC(50) = approximately 10-50 microM), transforming growth factor-beta1 (TGF-beta1; IC(50) = approximately 100-200 microM), and interleukin-8 (IC(50) = approximately 100 microM) formation, but had no effect on tumor necrosis factor-alpha. Interleukin-12 and -18-induced interferon-gamma formation by monocytes was also attenuated by tranilast. A23187-induced monocyte leukotriene C(4) or PGE(2) formation was inhibited by tranilast at IC(50) values of 10-40 microM and 2-20 microM, respectively, incubated with or without exogenous arachidonic acid. Interestingly, tranilast (up to 1000 microM) had no direct effects on cyclooxygenase I or II activity, nor did it have significant effects on human type IIA 14 kDa or type IV 85 kDa phospholipase A(2) activity. Furthermore, tranilast had no effect on endotoxin-induced cyclooxygenase II protein expression, suggesting tranilast modulates eicosanoid production and release by an as yet unidentified mechanism. Alternatively, the expression of TGF-beta1 was inhibited by tranilast but found to be due in part to inhibition of PGE(2) because exogenous PGE(2) could abrogate tranilast-mediated inhibition of TGF-beta1. Taken together, although a reported direct inhibitor of fibroblast proliferation, we show tranilast also attenuates the proinflammatory activity of human monocytes, adding to its potential efficacy as a therapeutic agent in restenosis.
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PMID:Modulation of human monocyte activities by tranilast, SB 252218, a compound demonstrating efficacy in restenosis. 1108 41