Inhibition of relaxations to nitrergic stimulation of the mouse anococcygeus by duroquinone

Abstract

(1 gM) and S-nitroso-glutathione (30 uM), but potentiated those to 8-Br-cyclic GMP (100 Mm).4 Neither hydroquinone (HQ; 100 MM) nor l,4-benzoquinone (BQ; 100 MM), 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.

Gastrointestinal Function Regulation by Nitrergic Efferent Nerves

“…Therefore, it is hypothesized that there are endogenous antioxidant defense mechanisms, enzymatic and nonenzymatic, for the neurotransmission process to be mediated by free NO. Similar conclusions were also obtained from studies using an irreversible inhibitor of superoxide dismutase (Martin et al, 1994;Lilley and Gibson, 1995;Paisley and Martin, 1996;Okamura et al, 1998a;Tanaka et al, 1999). Goyal and He (1998) noted that nitrergic slow IJP and hyperpolarization evoked by the NO ⅐ redox donor, diethylenetriamine/NO adduct, were suppressed by guanylyl cyclase inhibitors but not by apamin in the guinea pig ileal circular muscle, whereas hyperpolarization caused by sodium nitroprusside and solubilized NO gas was antagonized by apamin but not by guanylyl cyclase inhibitors.…”

Effect of thiol modulators and Cu/Zn superoxide dismutase inhibition on nitrergic relaxations in the rat gastric fundus

“…These results might suggest that antioxidant enzymes may have an important protective role on the NO-mediated neurotransmission. This was recently illustrated by the finding that an inhibitor of Cu/Zn SOD made the nitrergic neurotransmitter sensitive to superoxides in the bovine retractor penis muscle and in the mouse anococcygeus muscle Lilley & Gibson, 1995;Paisley et al, 1996). In addition, in bioassay experiments, we previously demonstrated that responses to the nitrergic neurotransmitter of the canine ileocolonic junction were inhibited by superoxide anion generators to an comparable extent as the responses to authentic NO, whereas those to nitrosothiols were not affected (Boeckxstaens et al, 1994;De Man et al, 1995b).…”

“…In a second series of experiments, the rat gastric fundus was treated for 2 h with the inhibitors of Cu/Zn superoxide dismutase (Cu/Zn SOD), diethyldithiocarbamate (1 mM, Martin et al, 1994;Lilley & Gibson, 1995) and triethylenetetramine (0.1 mM, Abdalla & Will, 1995). After wash-out, the effect of this treatment in the presence and absence of pyrogallol or duroquinone was investigated on the frequency-response curve to electrical stimulation (1-8 Hz, 1 ms), on the concentrationresponse curve to NO (0.03-3 pM) and on the relaxation to ATP (10 gM).…”

“…However, in different studies that were carried out in a variety of tissues, the exact identity of the nitrergic NANC neurotransmitter was questioned. A number of pharmacological compounds had a different effect on responses to authentic NO and on responses to NANC nerve stimulation (Gillespie & Sheng, 1990;Hobbs et al, 1991;Barbier & Lefebvre, 1992;Jenkinson et al, 1995;Lilley & Gibson, 1995;Rand & Li, 1995), suggesting that the nitrergic NANC neurotransmitter is not free NO but an NO-releasing compound such as a nitrosothiol (Gibson et al, 1992;Thornbury et al, 1991;Kerr et al, 1992;Kitamura et al, 1993;Barbier & Lefebvre, 1994;Liu et al, 1994). An alter-native explanation for this differential effect is that the nitrergic neurotransmitter is free NO which is protected from breakdown by tissue antioxidants such as superoxide dismutase (SOD), which scavenges superoxide radicals.…”

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

“…However, they did not examine the property of nitrergic nerve in vasculature. On the other hand, it was noted that treatment with diethyldithiocarbamate, a membrane-permeable inhibitor of Cu/Zn SOD, allowed pyrogallol, hydroquinone, and duroquinone to inhibit the NO-mediated neurogenic response in the bovine retractor penis muscle and mouse anococcygeus muscle Lilley and Gibson, 1995). The inhibition was reversed by FIG.…”