Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible mechanism of immunosuppressive effect of emodin (1,3,8-trihydroxy-6-methylanthraquinone) was investigated in this study. Human mononuclear cells (10(6) cells/ml) were stimulated with 0.25% phytohemagglutinin for 24, 48 and 72 h, and the proliferative response was determined by the uptake of tritiated thymidine. In the presence of emodin (10(-6) to 3 x 10(-5) M), the proliferative response was reduced in a dose-dependent manner. Emodin (3 x 10(-7) to 3 x 10(-5) M) also dose dependently reduced the proliferative response to mixed lymphocyte reaction. After 72 h exposure to emodin (10 microM), interleukin-1 (IL-1), interleukin-2 (IL-2) production and IL-2 receptor expression were all reduced. The structure-activity relationship of emodin and 10 other anthraquione derivatives indicates that the free hydroxyl group at the beta-position of the anthraquinone nucleus plays an important role in the immunosuppressive effect. The suppressive activity of emodin was significantly inhibited by catalase (a scavenger of hydrogen peroxide), but little affected by superoxide dismutase (a scavenger of superoxide radical) and mannitol (a scavenger of hydroxyl radical). Methylene blue and hemoglobin, guanylate cyclase inhibitors, did not significantly affect the suppressive activity of emodin. Nordihydroguaiaretic acid (a lipoxygenase inhibitor) significantly potentiated the suppressive activity whereas quinacrine (a phospholipase A2 inhibitor) and indomethacin (a cyclooxygenase inhibitor) did not significantly affect it. The results suggest that the immunosuppressive effect of emodin may be partly mediated through hydrogen peroxide generated from semiquinone and regulated by arachidonic acid metabolites or byproducts.
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PMID:Immunosuppressive effect of emodin, a free radical generator. 153 96

The possible mechanism underlying the vasorelaxant effect of emodin isolated from a Chinese herb, was investigated in this study. Emodin dose dependently relaxed isolated vascular rings of human internal mammary artery and saphenous vein, rabbit thoracic aorta, abdominal aorta and mesenteric artery, and rat thoracic aorta. There were no differences in the sensitivity (IC50) and maximal relaxation between intact and endothelium-denuded preparations of rat aorta. In the presence of emodin (10 microM), the contractile responses of rat aorta to phenylephrine, serotonin and potassium chloride were depressed. The relaxation response to acetylcholine was attenuated by emodin, whereas that to isoproterenol was unaffected. The relaxation response to emodin was inhibited by free radical scavengers, superoxide dismutase, catalase and mannitol, and guanylate cyclase inhibitors, methylene blue and hemoglobin. Catalase was the most effective scavenger. Quinacrine (phospholipase A2 inhibitor), indomethacin (cyclooxygenase inhibitor) and nordihydroguaiaretic acid (NDGA, lipoxygenase inhibitor) potentiated the relaxation induced by emodin. NDGA was the most effective potentiator. Exposure of aortic rings to emodin (10 microM) increased the basal level of guanosine 3',5'-cyclic monophosphate (cGMP). It is suggested that the vasorelaxant effect of emodin may be mainly due to cGMP accumulation as a result of guanylate cyclase activation by free radicals and/or hydrogen peroxide generated from semiquinone.
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PMID:Vasorelaxant effect of emodin, an anthraquinone from a Chinese herb. 166 13

1. Acetylcholine, ionophore A23187 and melittin induced endothelium-dependent relaxations of preconstricted strips of rabbit aorta. These relaxations are likely to be mediated by endothelium-derived relaxing factor (EDRF). 2. Relaxations in response to acetylcholine (1 microM) were inhibited by the following lipoxygenase inhibitors, with the approximate IC50 values indicated in parentheses: gossypol (1.5 microM), nordihydroguairetic acid (NDGA, 5 microM), AA 861 (20 microM), phenidone (30 microM), quercetin (40 microM), BW 755C (300 microM), and piriprost (500 microM); with cirsiliol 50% inhibition was not achieved. Acetylcholine-induced relaxations were also blocked by the cytochrome P-450-mono-oxygenase inhibitors proadifen (SKF 525A, 4 microM), metyrapone (300 microM), and cimetidine (300 microM); 7,8 benzoflavone had no effect up to 100 microM. 3. The more potent inhibitors were also tested against relaxations induced by A23187 (0.1 microM) and melittin (1 microM) and produced partial inhibition of these relaxations. 4. The mechanism of action of the more potent inhibitors was investigated in a bioassay system. EDRF was produced in columns filled with cultured human endothelial cells. The factor was bioassayed with endothelium denuded segments of rabbit femoral artery. When added to effluent of the column, NDGA, AA861, proadifen and metyrapone inhibited the EDRF-induced vasodilatation, whereas gossypol had no effect. Gossypol, however, blocked EDRF production when infused through the column. 5. The more potent inhibitors were also tested to determine their effect on purified soluble guanylate cyclase. While gossypol, NDGA and proadifen had no appreciable effects, basal and nitroprusside (50 microM)-stimulated guanylate cyclase activity was inhibited by AA861 and metyrapone. 6. These data suggest that many of the above compounds inhibit EDRF by mechanisms other than lipoxygenase- or cytochrome P-450-mono-oxygenase inhibition.
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PMID:Mechanisms of action of lipoxygenase and cytochrome P-450-mono-oxygenase inhibitors in blocking endothelium-dependent vasodilatation. 289 18

The vascular endothelium appears obligatory for the expression of the vasodilating property of most polypeptides. A number of polypeptides were studied on the rat aortic ring preparation which was pre-contracted with phenylephrine and only basic polypeptides containing one or more arginine residues elicited relaxation which was endothelium dependent. These peptides included melittin and poly-L-Arg. The basic polypeptide poly-L-Lys also elicited endothelium dependent relaxation, but to a lesser extent than arginine containing polypeptides. Two basic polypeptides, apamin and mastoparan do not promote endothelium dependent relaxation. The former contains arginine between disulfide bonds and in the latter arginine is absent. Basic amino acids and dipeptides which contain arginine, and also polyamines did not elicit relaxation even at high concentrations (10(-3) M). The relaxation elicited by melittin, poly-L-Arg and poly-L-Lys was inhibited by ETYA, NDGA, p-bromophenacyl bromide and not by indomethacin. Methylene blue, an inhibitor of soluble guanylate cyclase, also abolished the relaxation. We suggest that arginine containing peptides may relax vascular smooth muscle by acting directly on the vascular smooth muscle (eg: atriopeptins) and/or or by eliciting release of a relaxing factor(s) from the endothelium.
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PMID:Endothelium dependent vascular relaxation by arginine containing polypeptides. 380 Oct 12