Effect of enzymatically generated reactive oxygen metabolites on the cyclic nucleotide content in isolated rat glomeruli.
Effect of enzymatically generated reactive oxygen metabolites on the cyclic nucleotide content in isolated rat glomeruli.
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酶促产生的活性氧代谢物对离体大鼠肾小球中环核苷酸含量的影响。
DOI：
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发表时间：
1984
影响因子：
15.9
通讯作者：
S. Shah
中科院分区：
文献类型：
--
作者：
S. Shah
在本研究中，我们检测了活性氧代谢产物（由黄嘌呤-黄嘌呤氧化酶系统产生）对从大鼠肾皮质分离的肾小球和小管中腺苷-3′，5′-环单磷酸腺苷（环AMP）和鸟苷-3′，5′-环单磷酸鸟苷（环GMP）含量的影响。黄嘌呤(0.1 mM)-黄嘌呤氧化酶（0.025 U/ml）显著提高肾小球中环AMP含量（P < 0.001），从18 +/- 1增加到50 +/- 4 pmol/mg蛋白（n = 13）。黄嘌呤氧化酶特异性抑制剂别嘌呤醇（10(-3)）可显著抑制该反应（δ %-74 +/- 9, n = 3）。黄嘌呤-黄嘌呤氧化酶系统对小管中环AMP含量、肾小球和小管中环GMP含量没有影响。这种缺乏反应并不是因为组织缺乏反应性，因为甲状旁腺激素导致小管中环AMP含量显著增加，硝普赛显著增加肾小球中环GMP含量。肾小球中环AMP的增加是由于活性氧代谢物的产生，而不是黄嘌呤-黄嘌呤氧化酶反应的其他产物（如尿酸）——在培养液中添加尿酸没有影响；使用另一种底物为黄嘌呤氧化酶，乙醛显著提高（δ % 112 +/- 7, n = 4, P < 0.001）环AMP含量；破坏过氧化氢的过氧化氢酶引起对黄嘌呤-黄嘌呤氧化酶反应的显著抑制（δ % -90 +/- 5, n = 4）。过氧化氢酶有明显的抑制作用，而超氧化物歧化酶没有作用（在完全清除超氧化物的浓度下），这表明过氧化氢是产生这种作用的氧代谢物。葡萄糖-葡萄糖氧化酶（一种直接产生过氧化氢的系统）和过氧化氢的直接添加导致肾小球中环AMP含量的剂量依赖性增加，这进一步支持了过氧化氢作为所观察到的效应的负责物质的作用。使用前列腺素合成抑制剂和血清素和组胺拮抗剂的其他实验表明，过氧化氢通过增强前列腺素合成来增加肾小球中环AMP的含量。
In the present study we examined the effect of reactive oxygen metabolites (generated by the xanthine-xanthine oxidase system), on adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanosine-3',5'-cyclic monophosphate (cyclic GMP) content in glomeruli and tubules that were isolated from rat renal cortex. Xanthine (0.1 mM)-xanthine oxidase (0.025 U/ml) significantly increased (P less than 0.001) the cyclic AMP content in glomeruli from 18 +/- 1 to 50 +/- 4 pmol/mg protein (n = 13). The response was dose dependent and was markedly inhibited (delta %-74 +/- 9, n = 3) by allopurinol (10(-3), a specific inhibitor of xanthine oxidase. Cyclic AMP content in the tubules, and the cyclic GMP content in glomeruli and tubules, were not altered by the xanthine-xanthine oxidase system. This lack of response was not due to lack of responsiveness of the tissues because parathyroid hormone caused a marked increase in the cyclic AMP content in tubules, and nitroprusside markedly increased the cyclic GMP content in glomeruli. The increase in cyclic AMP in glomeruli was due to generation of reactive oxygen metabolites rather than of other products (e.g. uric acid) of the xanthine-xanthine oxidase reaction--addition of uric acid to incubations had no effect; using another substrate for xanthine oxidase, acetaldehyde significantly increased (delta % 112 +/- 7, n = 4, P less than 0.001) the cyclic AMP content; and catalase that destroys hydrogen peroxide caused a marked inhibition (delta % -90 +/- 5, n = 4) of the response to xanthine-xanthine oxidase. The marked inhibition by catalase, and the lack of effect of superoxide dismutase (in a concentration that completely scavenged superoxide) suggested hydrogen peroxide as the responsible oxygen metabolite for the observed effect. Glucose-glucose oxidase (a system that directly generates hydrogen peroxide), and direct addition of hydrogen peroxide caused a dose-dependent increase in the cyclic AMP content in glomeruli, which further supports the role of hydrogen peroxide as the responsible species for the observed effect. Additional experiments that used prostaglandin synthesis inhibitors and antagonists of serotonin and histamine suggested that hydrogen peroxide increases cyclic AMP content in glomeruli by enhancing prostaglandin synthesis.
影响因子：
15.9
作者：
HOLDSWORTH, SR;NEALE, TJ;WILSON, CB
通讯作者：
WILSON, CB
布洛芬对内皮和血小板前列腺素合成的比较影响。
DOI：
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发表时间：
1981
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Parks,WM;Hoak,JC;Czervionke,RL
通讯作者：
Czervionke,RL