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

In order to demonstrate the localization of an anti-allergic agent, Tranilast, in the mast cells, light microscopic radioautography was performed. The mast cells collected from rat peritoneal cavity were incubated for 0 to 60 min in a medium containing 3H-Tranilast. After the incubation, they were fixed, embedded and processed for light microscopic radioautography. The radioautographic silver grains were frequently localized around and over the cytoplasmic granules and their number increased according to the prolongation of incubation time. From the results obtained at present it was demonstrated that Tranilast was rapidly taken into the cytoplasm of mast cells. This phenomenon may suggest an important role of this agent in the inhibition of allergic reactions of mast cells.
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PMID:Light microscopic radioautographic study of the localization of an anti-allergic agent, Tranilast, in rat mast cells. 245 76

The cytomorphologic features of voided urine specimens from two patients with antiallergic drug (Tranilast)-induced eosinophilic cystitis are described. The urothelial cells tend to occur in clusters and are of variable size. The remarkable vacuolization is observed in the cytoplasm. The markedly vacuolated cytoplasm which may be infiltrated by polymorpho-nuclear leucocytes is unremarkable. Some nuclei usually show transparent center surrounded by a rim of chromatin. The nucleoli are prominent. Marked vacuoles in the nucleus is observed. These findings are very important cytomorphologic characteristics for differential diagnosis between eosinophilic cystitis and malignant bladder tumor and cystitis due to bacterial infection.
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PMID:Cytomorphologic features of antiallergic drug-induced eosinophilic cystitis with bronchial asthma. 245 Aug 24

We investigated the mechanism of inhibitory action of tranilast on chemical mediator release by antigen-antibody reactions. Tranilast (10(-5)-10(-3) M) inhibited antigen (DNP-Ascaris)-induced histamine release from sensitized purified rat mast cells (PMC), but did not show an obvious influence on intracellular cyclic AMP. 45Ca uptake into PMC induced by antigen (300 micrograms/ml) was obviously suppressed by tranilast (10(-6)-10(-3) M). Tranilast (10(-4) M) inhibited antigen-induced histamine release from and 45Ca uptake into PMC independently of the presence or absence of glucose in the medium. On the other hand, 2-deoxyglucose (10(-2) M) markedly inhibited both responses in the absence but not in the presence of glucose. Tranilast slightly inhibited Ca-induced contraction of guinea pig taenia coli, but had no influence on aggregation of rabbit platelets. Verapamil (10(-6)-10(-4) M) had no effect on antigen-induced histamine release, but it markedly suppressed Ca-induced contraction and platelet aggregation. From these results, we suggest that the mechanism of inhibitory action of tranilast on the release of antigen-induced chemical mediator from mast cells involves the suppression of Ca uptake, but that its mode of action is apparently different from those of 2-deoxyglucose and verapamil.
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PMID:Study of the mechanism of inhibitory action of tranilast on chemical mediator release. 245 12

Degranulation of IgE-sensitized rat mast cells by antigen was studied quantitatively in vitro and in vivo by electron microscopy. The inhibition of this degranulation by an anti-allergic drug, N-(3,4-dimethoxycinnamoyl)anthranilic acid (Tranilast), was also examined both in vitro and in vivo. In the in vitro study using peritoneal mast cells, alteration of the granules, cavity formation by fusion of the perigranular membrane and granule discharge due to fusion of the cavity membrane with the cell membrane were observed and were accompanied by histamine release. Scanning electron microscopy disclosed the extrusion of smooth, round bodies from pores formed on the cell surface. In the in vivo study of passive cutaneous anaphylaxis (PCA), the characteristic features of mast cell degranulation were obvious 5 min after the injection of antigen; leakage of dye increased progressively from 5 to 30 min but was not found at 6 h. From quantitative analysis of the substructure of mast cells, it was demonstrated that degranulation of IgE-sensitized mast cell induced by antigen was achieved by sequential exocytosis both in vitro and in vivo. Tranilast inhibited these changes to a remarkable extent and it was concluded that the inhibition of mast cell degranulation by this drug might play an important role in anti-allergic treatment.
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PMID:Mast cell degranulation and its inhibition by an anti-allergic agent tranilast. An electron microscopic study. 245 82

We encountered 8 cases of cystitis probably caused by Tranilast. Bladder biopsy performed on 6 of the 8 cases revealed eosinophilic cystitis in 3 cases. In the lymphocyte stimulation test using Tranilast as an antigen, a positive and false positive reaction was seen in one case each. This disease seemed to occur as a result of allergy of the bladder specific to Tranilast.
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PMID:[Cystitis in 8 patients treated with tranilast]. 245 39

The molecular basis for the inhibitory action of the antiatopic drug, N-(3',4'-dimethoxycinnamoyl)anthranilic acid (Tranilast), on the thrombin-induced release of a lysosomal enzyme, beta-N-acetylglucosaminidase, from washed rabbit platelets was investigated. Tranilast dose dependently increased cyclic AMP and cyclic GMP levels in thrombin-stimulated platelets, parallel with the inhibition of beta-N-acetylglucosaminidase release. There was no significant effect of Tranilast on adenylate or guanylate cyclase activity. Tranilast inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterases in a cell-free system. The data suggest that the inhibitory action of Tranilast on the release reaction in platelets was due at least in part to inhibition of cyclic nucleotide phosphodiesterases followed by an elevation of cyclic AMP and cyclic GMP levels.
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PMID:The mechanism for the inhibitory action of N-(3',4'-dimethoxycinnamoyl)anthranilic acid (tranilast) on the release reaction in platelets. 246 71

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

In order to demonstrate the localization associated with metabolism of an anti-allergic agent, Tranilast, in the liver, light microscopic radioautography of the liver was performed. Rats were administrated orally with 3H-Tranilast, and were sacrificed at 15 minutes to 24 hours after the administration. The livers were taken out and fixed, embedded and processed for light microscopic radioautography. 3H-Tranilast was absorbed rapidly, and the radioactivity in the liver increased and decreased within several hours. The number of radioautographic silver grains reached a maximum 3 hours after the administration. From 1 to 6 hours after the administration, the silver grains decreased from the portal area toward the central area. Seventy to 80% of all silver grains on the hepatocytes were retained in the cytoplasms of the hepatocytes at any experimental period. From these results, it was concluded that the localization of radioautographic silver grains was associated with Tranilast uptake of hepatocytes in each hepatic lobular compartment and that the metabolic process from uptake to excretion of Tranilast took part in the hepatocytes in each hepatic lobular compartment.
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PMID:Radioautographic study on the localization of an anti-allergic agent, tranilast, in the rat liver. 247 16

Tranilast is an oral antiallergic agent developed in Japan. This study investigated the effect of prolonged administration of Tranilast on the bronchial sensitivity of 18 asthmatic subjects. They were treated for either less than 3 months or more than 3 months continuously. Methacholine loading testing was used to assess bronchial reactivity, and the respiratory parameters were recorded on an Astograph. Patients treated for longer than 3 months showed a significant decrease in bronchial sensitivity (p less than 0.05). The anticholinergic and bronchodilatory properties of Tranilast were also investigated in 8 subjects. No significant anticholinergic or bronchodilatory effects were observed following a single oral dose of 100 mg of Tranilast.
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PMID:The effects of long term Tranilast administration on bronchial hypersensitivity in asthmatics. 247 86


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