Effects of pyrogallol, hydroquinone and duroquinone on responses to nitrergic nerve stimulation and NO in the rat anococcygeus muscle

被引:19
作者
La, M [1 ]
Rand, MJ [1 ]
机构
[1] Royal Melbourne Inst Technol, Dept Med Lab Sci, Pharmacol Res Unit, Melbourne, Vic 3001, Australia
关键词
anococcygeus muscle (rat); diethyldithiocarbamic acid (DETCA); duroquinone; hydroquinone; nitrergic transmission; nitric oxide; pyrogallol; superoxide dismutase;
D O I
10.1038/sj.bjp.0702277
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The hypothesis that endogenous superoxide dismutase (SOD) protects the nitrergic transmitter from inactivation by superoxide and that this explains the lack of sensitivity of the transmitter to superoxide generators was tested in the rat isolated anococcygeus muscle. 2 Responses to nitrergic nerve stimulation or to NO were not significantly affected by exogenous SOD or by the Cu/Zn SOD inhibitor diethyldithiocarbamic acid (DETCA). 3 Hydroquinone produced a concentration-dependent reduction of responses to NO with an IC50 of 27 mu M, and higher concentrations reduced relaxant responses to nitrergic nerve stimulation with an IC50 of 612 mu M. The effects of hydroquinone were only slightly reversed by SOD, so it does not appear to be acting as a superoxide generator. 4 Pyrogallol produced a concentration-dependent reduction in responses to NO with an IC50 value of 39 mu M and this effect was reversed by SOD (100-1000 u ml(-1)). Pyrogallol did not affect responses to nitrergic nerve stimulation. Treatment with DETCA did not alter the differentiating action of pyrogallol. 5 Duroquinone produced a concentration-dependent reduction of relaxations to NO with an IC50 value of 240 mu M and 100 mu M slightly decreased nitrergic relaxations. After treatment with DETCA, duroquinone produced greater reductions of relaxant responses to NO and to nitrergic stimulation, the IC50 values being 8.5 mu M for NO and 40 mu M for nitrergic nerve stimulation: these reductions were reversed by SOD. 6 The findings do not support the hypothesis that the presence of Cu/Zn SOD explains the greater susceptibility of NO than the nitrergic transmitter to the superoxide generator pyrogallol, but suggest that it may play a role in the effects of duroquinone.
引用
收藏
页码:342 / 348
页数:7
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