Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effect of nipradilol on contraction of the posterior ciliary artery induced by high potassium or norepinephrine and on cyclic GMP (cGMP) levels in the posterior ciliary artery of dogs. Nipradilol caused dose-dependent relaxation of KCl-and norepinephrine-induced contractions of posterior ciliary artery. The relaxant effect of nipradilol on norepinephrine-contracted ciliary artery was significantly greater than that on KCl-contracted ciliary artery. In KCl-contracted ciliary artery, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) M) did not alter the relaxant effect of nipradilol, whereas 1H-1,2,4-oxadiazolo-4,3-a-quinoxalin-1-one (ODQ, 10(-6) M) significantly inhibited this effect. Ethacrynic acid at 10(-5) M, sulfasalazine at 10(-4) M and S-decylglutathione at 10(-4) M (glutathione S-transferase inhibitors) did not inhibit the relaxant effect of nipradilol. In addition, nipradilol produced dose-dependent increases in cGMP levels in the canine posterior ciliary artery. These findings indicate that nipradilol-induced vasorelaxation in the canine posterior ciliary artery occurs via stimulation of the guanylyl cyclase-cGMP pathway.
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PMID:Nipradilol induces vasodilation of canine isolated posterior ciliary artery via stimulation of the guanylyl cyclase-cGMP pathway. 1209 33

BACKGROUND:: Nipradilol (3,4-dihydro-8-[2-hydroxy-3-isopropyl-amino]propoxy-3-nitroxy-2-H-1-benzopyran), a potent non-selective beta-adrenoceptor antagonist, has been shown to increase NO production. The mechanisms are up-regulation of nitric oxide synthase (NOS) and direct release of NO from nipradilol. The process of direct NO release from nipradilol requires a reductase, such as glutathione S-transferase (GST) in some cells but non-enzymatic NO release was reported in pig coronary arteries. Direct NO release from nipradilol in human coronary arteries has not been examined yet, though this information is of importance. PURPOSE:: To demonstrate direct NO release from nipradilol in human coronary arterial smooth muscle cells (HCASMC) by using a fluorescent NO probe (DAF-2) and an NO-electrode. METHODS AND RESULTS:: HCASMC were loaded with DAF-2 and images of fluorescence (515nm) were obtained under excitation at 488nm through an intensified CCD with an inverted phase-contrast microscope. Concomitantly, NO was measured using an NO-electrode (0.2mm o.d.; 501, Inter Medical Co. Ltd., Nagoya, Japan) after addition of various concentrations of nipradilol (1, 5 or 10microM) with or without ethacrynic acid (GST inhibitor). The cells showed no fluorescence at baseline, but intense fluorescence appeared at 30min after addition of 10microM nipradilol. The intensities of fluorescence at 30min in the control, nipradilol and nipradilol with ethacrynic acid groups were 98 +/- 6, 163 +/- 10 and 128 +/- 6% of the baseline level, respectively. Ethacrynic acid itself did not affect the fluorescence. Continuous measurements of NO by the electrode showed the NO generation peaked at about 30min, remained at the same level till about 45min and then gradually declined. Nipradilol did not produce NO at all in the absence of cells. The dose-dependency study of NO release from nipradilol showed 45 +/- 12, 72 +/- 24 and 157 +/- 23nM, respectively, at 1, 5 and 10microM nipradilol. All experiments were performed under conditions where endogenous formation of NO was inhibited by an NOS inhibitor (10(-4)M N(G)-monomethyl-l-arginine (l-NMMA)). CONCLUSION:: Nipradilol can release NO in the presence of human coronary arterial smooth muscle cells and the denitration reaction catalyzed by a reductase such as glutathione S-transferase contributes substantially to NO release from nipradilol.
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PMID:Direct nitric oxide release from nipradilol in human coronary arterial smooth muscle cells observed with fluorescent NO probe and NO-electrode. 1536 17

Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)propoxy-3-nitroxy-2H-1-benzopyran) is used clinically as an anti-glaucoma ophthalmic solution in Japan, and was recently reported to suppress N-methyl-d-aspartate-induced retinal damage in rats. Here we investigated cytotoxic and cytoprotective actions of nipradilol on primary cultures of rat cortical neurons. Treatment of cortical cultures with a high concentration (500 microM) of nipradilol significantly reduced cell viability, increased lactate dehydrogenase (LDH) release and nitrite concentration in culture medium, whereas desnitro-nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)propoxy-3-hydroxy-2H-1-benzopyran) had no significant effects. Nipradilol-induced neuronal damage was inhibited by S-hexylglutathione, a glutathione S-transferase inhibitor, and FeTPPS (5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride), a peroxynitrite decomposition catalyst. On the other hand, relatively low concentrations (10-100 microM) of nipradilol but not desnitro-nipradilol prevented neuronal cell death induced by 24 h application of 100 microM glutamate. Importantly, neuroprotective concentration (100 microM) of nipradilol suppressed glutamate-induced elevation of intracellular Ca2+ concentrations, but had no effect on intracellular cyclic GMP levels. Hence, nipradilol can protect cultured cortical neurons against glutamate neurotoxicity via cyclic GMP-independent mechanisms, and nitric oxide (NO) released from the nitoroxy moiety of nipradilol may mediate neuroprotective effect through the modulation of NMDA receptor function.
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PMID:Nitric oxide-mediated effect of nipradilol, an alpha- and beta-adrenergic blocker, on glutamate neurotoxicity in rat cortical cultures. 1651 84