7-乙氧基试卤灵对一氧化氮介导反应的抑制作用，7-乙氧基试卤灵是细胞色素P450的一种底物和竞争性抑制剂。

Inhibition of NO-medicate responses by 7-ethoxyresorufin, a substrate and competitive inhibitor of cytochrome P450.

作者信息

Li C G, Rand M J

机构信息

Department of Medical Laboratory Science, Royal Melbourne Institute of Technology, Victoria, Australia.

出版信息

Br J Pharmacol. 1996 May;118(1):57-62. doi: 10.1111/j.1476-5381.1996.tb15366.x.

DOI:10.1111/j.1476-5381.1996.tb15366.x

PMID:8733576

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1909496/

Abstract

The effects of 7-ethoxyresorufin (7-ER), which is a substrate for and competitive inhibitor of cytochrome P450, were studied on responses to nitric oxide (NO), the NO donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), acetylcholine-induced endothelium-dependent relaxations of rat and rabbit aortic rings and nitrergic nerve stimulation-induced relaxations of rat anococcygeus muscles. 2. In rat and rabbit aortic rings, 7-ER (2 microM) inhibited the relaxations to acetylcholine in endothelium-intact preparations and the relaxant action of NO in endothelium-denuded preparations. Relaxant responses to SNP and GTN were inhibited by 7-ER in the rat but not rabbit aortic rings. However, the relaxant actions of papaverine and 8-bromo-cyclic GMP were not affected by 7-ER. 3. In rat anococcygeus muscles, 7ER (2 microM) inhibited the relaxant action of NO, but relaxations elicited by nitrergic nerve stimulation were only partly inhibited by a higher concentration of 7-ER (10 microM). 4. After inhibition by 7-ER, superoxide dismutase (100 u ml-1) restored NO-induced relaxations of the rat aortic rings, but not acetylcholine-, SNP or GTN-induced relaxations, and restored NO- and nitrergic nerve stimulation-induced relaxations of anococcygeus muscles. 5. Another cytochrome P450 inhibitor, troleandomycin (10-30 microM), had no effect on NO- or acetylcholine-induced relaxations of rat aortic rings and NO- or nitrergic nerve stimulation-induced relaxations of anococcygeus muscles. However, resorufin, an analogue of 7-ER, inhibited responses to acetylcholine, NO and GTN in rat aortic rings. 6. The results suggest that 7-ER inhibited responses to NO and nitrergic nerve stimulation through generation of superoxide radicals. However, an additional mechanism may be involved in the reduction in acetylcholine-induced response in aortic rings. 7. A 7-ER sensitive P450 system may be involved in the bioactivation of GTN and SNP in rat aortic rings, but not in rabbit aorta or rat anococcygeus muscles.

摘要

研究了细胞色素P450的底物及竞争性抑制剂7-乙氧基试卤灵（7-ER）对一氧化氮（NO）、NO供体硝普钠（SNP）和硝酸甘油（GTN）、乙酰胆碱诱导的大鼠和兔主动脉环内皮依赖性舒张以及含氮能神经刺激诱导的大鼠肛尾肌舒张反应的影响。2. 在大鼠和兔主动脉环中，7-ER（2微摩尔）抑制内皮完整制剂中对乙酰胆碱的舒张反应以及内皮剥脱制剂中NO的舒张作用。7-ER抑制大鼠主动脉环中对SNP和GTN的舒张反应，但对兔主动脉环无此作用。然而，7-ER不影响罂粟碱和8-溴环鸟苷酸的舒张作用。3. 在大鼠肛尾肌中，7-ER（2微摩尔）抑制NO的舒张作用，但含氮能神经刺激引起的舒张仅被更高浓度的7-ER（10微摩尔）部分抑制。4. 被7-ER抑制后，超氧化物歧化酶（100单位/毫升）恢复了NO诱导的大鼠主动脉环舒张，但未恢复乙酰胆碱、SNP或GTN诱导的舒张，且恢复了NO和含氮能神经刺激诱导的肛尾肌舒张。5. 另一种细胞色素P450抑制剂三乙酰竹桃霉素（10 - 30微摩尔）对大鼠主动脉环中NO或乙酰胆碱诱导的舒张以及肛尾肌中NO或含氮能神经刺激诱导的舒张无影响。然而，7-ER的类似物试卤灵抑制大鼠主动脉环中对乙酰胆碱、NO和GTN的反应。6. 结果表明，7-ER通过产生超氧自由基抑制对NO和含氮能神经刺激的反应。然而，主动脉环中乙酰胆碱诱导反应降低可能涉及另一种机制。7. 7-ER敏感的P450系统可能参与大鼠主动脉环中GTN和SNP的生物活化，但不参与兔主动脉或大鼠肛尾肌中的生物活化。