British Journal of Pharmacology

January 1999, Volume 126, Issue 1, Pages 342 - 348

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

Mylinh La2 & Michael J. Rand1

Pharmacology Research Unit, Department of Medical Laboratory Science, Royal Melbourne Institute of Technology, GPO Box 2476V, Melbourne 3001, Australia    

1Author for correspondence E-mail: miker@rmit.edu.au


2Current address: Dr Mylinh La, Insitut für Pharmakologie und Toxikologie, Julius-Maximilian University, Versbacherstr. 9, W-97078 Würzburg, Germany



Keywords
Anococcygeus muscle (rat);   diethyldithiocarbamic acid (DETCA);   duroquinone;   hydroquinone;   nitrergic transmission;   nitric oxide;   pyrogallol;   superoxide dismutase

Abstract

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 µM, and higher concentrations reduced relaxant responses to nitrergic nerve stimulation with an IC50 of 612 µM. 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 µM 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 µM and 100 µM 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 µM for NO and 40 µM 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.

Received 28 September 1998; Accepted 6 October 1998

© Macmillan Publishers Ltd 1999