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Inhibition of relaxations to nitrergic stimulation of the mouse anococcygeus by duroquinone
Author(s) -
Lilley Elliot,
Gibson Alan
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15129.x
Subject(s) - chemistry , xanthine oxidase , sodium nitroprusside , superoxide , superoxide dismutase , nitric oxide , stimulation , penicillamine , biochemistry , endocrinology , enzyme , medicine , organic chemistry
1 The role of copper/zinc superoxide dismutase (Cu/Zn SOD) in protection of nitrergic neurotransmission in the mouse anococcygeus was investigated by use of duroquinone (DQ), which generates superoxide anions within tissues via reduction by flavoprotein enzymes. 2 In control anococcygeus muscles, DQ (10–100 μ m ) produced concentration‐related inhibition (‐log IC 40 =4.41) of relaxations to exogenous nitric oxide (NO; 15 μ m ). Nitrergic relaxations induced by field stimulation (10 Hz; 10 s train) were much less affected, 100 μ m DQ reducing nitrergic relaxations by only 14 ± 6%. 3 Following incubation with the Cu/Zn SOD inhibitor, diethyldithiocarbamate (DETCA; 3 mM; 45 min incubation; 10 min washout), the inhibitory effects of DQ on relaxations to NO were potentiated (‐log IC 40 = 5.22), and clear, concentration‐related inhibitions of nitrergic relaxations were now observed (‐log IC 40 = 4.54). In both cases, these inhibitions were partially reversed by Cu/Zn SOD (250 u ml −1 ). In DETCA‐treated tissues, DQ (100 μ m ) also reduced relaxations to sodium nitroprusside (1 μ m ) and S‐nitroso‐glutathione (30 μ m ), but potentiated those to 8‐Br‐cyclic GMP (100 μ m ). 4 Neither hydroquinone (HQ; 100 μ m ) nor 1,4‐benzoquinone (BQ; 100 μ m ), both of which reduced responses to exogenous NO, inhibited relaxations induced by field stimulation in DETCA‐treated tissues. Indeed, when added during DQ‐induced inhibition of nitrergic relaxations, both HQ and BQ produced partial reversal of the block. 5 DQ had no effect on the detection of superoxide anions estimated via the xanthine: xanthine oxidase chemiluminescence assay, or of authentic NO as measured by a chemical microsensor. However, the detection of both superoxide anions and NO in these assays was inhibited by inclusion of either HQ or BQ. 6 The results support the proposal that nitrergic transmission in the peripheral nervous system is protected by Cu/Zn SOD activity in the region of the neuroeffector junction, and this may explain the lack of effect of superoxide anion generating drugs such as DQ. Such an explanation does not hold for either HQ or BQ, which appear to be acting directly as free radical scavengers in these experiments.