Influence of Superoxide Dismutase Inhibition on the Discrimination Between NO and the Nitrergic Neurotransmitter in the Rat Gastric Fundus

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1996 Aug 1

PMID 8864558

Citations 8

Authors

R A Lefebvre

Affiliations

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Abstract

1. The influence of diethyldithiocarbamate (DETCA), that irreversibly inhibits Cu/Zn-containing superoxide dismutase, on the inability of 6-anilino-5,8-quinolinedione (LY83583), hypoxanthine/xanthine oxidase, hydroquinone and hydroxocobalamin to reduce electrically-induced NANC relaxations in the rat gastric fundus was investigated. 2. Longitudinal muscle strips of the rat gastric fundus were mounted for auxotonic recording in the presence of atropine and guanethidine and tone was raised by administration of prostaglandin F2 alpha DETCA (3 x 10(-3) M) slightly reduced the short-lasting relaxations induced by 10(-5) M exogenous nitric oxide (NO) and transmural electrical stimulation for 10 s at 4 Hz but this effect was not influenced by 1000 u ml-1 superoxide dismutase (SOD). 3. DETCA (3 x 10(-5) -3 x 10(-3) M) concentration-dependently potentiated the inhibitory effect of LY83583 upon the electrically-induced relaxations, although this was less pronounced than the inhibition of the NO-induced relaxations. The inhibition of the electrically-induced non-adrenergic non-cholinergic (NANC) relaxations was not reversed by SOD while that of the NO-induced relaxations was partially reversed. 4. The inhibitory effect of hypoxanthine/xanthine oxidase, hydroquinone and hydroxocobalamin on the electrically-induced NANC relaxations in the presence of DETCA (3 x 10(-3) M) was not different from the inhibitory effect of DETCA alone. 5. It was concluded that the differentiating effect of LY83583 between exogenous NO and the endogenous nitrergic neurotransmitter is partially related to protection of the endogenous nitrergic neurotransmitter by high levels of intracellular superoxide dismutase. This mechanism does not hold for hydroquinone and hydroxocobalamin, as they still discriminate between exogenous NO and the endogenous nitrergic neurotransmitter in the presence of DETCA. The possibility that the endogenous nitrergic neurotransmitter is not free NO in the rat gastric fundus therefore remains open.

Citing Articles

Influence of antioxidant depletion on nitrergic relaxation in the pig gastric fundus.

Colpaert E, Timmermans J, Lefebvre R Br J Pharmacol. 2002; 135(4):917-26.

PMID: 11861319 PMC: 1573215. DOI: 10.1038/sj.bjp.0704553.

Pre- and postjunctional protective effect of neocuproine on the nitrergic neurotransmitter in the mouse gastric fundus.

DE Man J, Moreels T, DE Winter B, Herman A, Pelckmans P Br J Pharmacol. 2001; 132(1):277-85.

PMID: 11156587 PMC: 1572530. DOI: 10.1038/sj.bjp.0703772.

Interaction of hypoxanthine/xanthine oxidase with nitrergic relaxation in the porcine gastric fundus.

Colpaert E, Lefebvre R Br J Pharmacol. 2000; 130(2):359-66.

PMID: 10807674 PMC: 1572077. DOI: 10.1038/sj.bjp.0703317.

Influence of bilirubin and other antioxidants on nitrergic relaxation in the pig gastric fundus.

Colpaert E, Lefebvre R Br J Pharmacol. 2000; 129(6):1201-11.

PMID: 10725269 PMC: 1571952. DOI: 10.1038/sj.bjp.0703176.

Effects of superoxide anion generators and thiol modulators on nitrergic transmission and relaxation to exogenous nitric oxide in the sheep urethra.

Garcia-Pascual A, Labadia A, Costa G, Triguero D Br J Pharmacol. 2000; 129(1):53-62.

PMID: 10694202 PMC: 1621122. DOI: 10.1038/sj.bjp.0703000.

References

Aimi Y, Kimura H, Kinoshita T, Minami Y, Fujimura M, Vincent S . Histochemical localization of nitric oxide synthase in rat enteric nervous system. Neuroscience. 1993; 53(2):553-60. DOI: 10.1016/0306-4522(93)90220-a. View

Berman R, Martin W . Arterial endothelial barrier dysfunction: actions of homocysteine and the hypoxanthine-xanthine oxidase free radical generating system. Br J Pharmacol. 1993; 108(4):920-6. PMC: 1908136. DOI: 10.1111/j.1476-5381.1993.tb13487.x. View

Barbier A, Lefebvre R . Influence of S-nitrosothiols and nitrate tolerance in the rat gastric fundus. Br J Pharmacol. 1994; 111(4):1280-6. PMC: 1910166. DOI: 10.1111/j.1476-5381.1994.tb14884.x. View

Liu X, Gillespie J, Martin W . Non-adrenergic, non-cholinergic relaxation of the bovine retractor penis muscle: role of S-nitrosothiols. Br J Pharmacol. 1994; 111(4):1287-95. PMC: 1910140. DOI: 10.1111/j.1476-5381.1994.tb14885.x. View

Boeckxstaens G, DE Man J, DE Winter B, Herman A, Pelckmans P . Pharmacological similarity between nitric oxide and the nitrergic neurotransmitter in the canine ileocolonic junction. Eur J Pharmacol. 1994; 264(1):85-9. DOI: 10.1016/0014-2999(94)90640-8. View

Wood J, Garthwaite J . Models of the diffusional spread of nitric oxide: implications for neural nitric oxide signalling and its pharmacological properties. Neuropharmacology. 1994; 33(11):1235-44. DOI: 10.1016/0028-3908(94)90022-1. View

Martin W, McAllister K, Paisley K . NANC neurotransmission in the bovine retractor penis muscle is blocked by superoxide anion following inhibition of superoxide dismutase with diethyldithiocarbamate. Neuropharmacology. 1994; 33(11):1293-301. DOI: 10.1016/0028-3908(94)90029-9. View

Ekblad E, Mulder H, Uddman R, Sundler F . NOS-containing neurons in the rat gut and coeliac ganglia. Neuropharmacology. 1994; 33(11):1323-31. DOI: 10.1016/0028-3908(94)90032-9. View

Kawada T, Ishibashi T, Sasage H, Kato K, Imai S . Modification by LY 83583 and methylene blue of relaxation induced by nitric oxide, glyceryl trinitrate, sodium nitroprusside and atriopeptin in aortae of the rat, guinea-pig and rabbit. Gen Pharmacol. 1994; 25(7):1361-71. DOI: 10.1016/0306-3623(94)90160-0. View

10.

Rand M, Li C . Nitric oxide as a neurotransmitter in peripheral nerves: nature of transmitter and mechanism of transmission. Annu Rev Physiol. 1995; 57:659-82. DOI: 10.1146/annurev.ph.57.030195.003303. View

11.

Jenkinson K, REID J, Rand M . Hydroxocobalamin and haemoglobin differentiate between exogenous and neuronal nitric oxide in the rat gastric fundus. Eur J Pharmacol. 1995; 275(2):145-52. DOI: 10.1016/0014-2999(94)00762-v. View

12.

Takahashi T, Owyang C . Vagal control of nitric oxide and vasoactive intestinal polypeptide release in the regulation of gastric relaxation in rat. J Physiol. 1995; 484 ( Pt 2):481-92. PMC: 1157909. DOI: 10.1113/jphysiol.1995.sp020680. View

13.

DE Man J, Boeckxstaens G, DE Winter B, Moreels T, Misset M, Herman A . Comparison of the pharmacological profile of S-nitrosothiols, nitric oxide and the nitrergic neurotransmitter in the canine ileocolonic junction. Br J Pharmacol. 1995; 114(6):1179-84. PMC: 1510352. DOI: 10.1111/j.1476-5381.1995.tb13331.x. View

14.

Lefebvre R . Nitric oxide in the peripheral nervous system. Ann Med. 1995; 27(3):379-88. DOI: 10.3109/07853899509002591. View

15.

Lilley E, Gibson A . Inhibition of relaxations to nitrergic stimulation of the mouse anococcygeus by duroquinone. Br J Pharmacol. 1995; 116(8):3231-6. PMC: 1909157. DOI: 10.1111/j.1476-5381.1995.tb15129.x. View

16.

Moncada S, Palmer R, Gryglewski R . Mechanism of action of some inhibitors of endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1986; 83(23):9164-8. PMC: 387095. DOI: 10.1073/pnas.83.23.9164. View

17.

BULBRING E, Tomita T . Catecholamine action on smooth muscle. Pharmacol Rev. 1987; 39(1):49-96. View

18.

Lefebvre R, Verplanken P, Bogaert M . Pharmacological characterization of the postjunctional beta-adrenoceptors in the rat gastric fundus. Eur J Pharmacol. 1984; 106(1):1-9. DOI: 10.1016/0014-2999(84)90671-x. View

19.

Abrahamsson H . Non-adrenergic non-cholinergic nervous control of gastrointestinal motility patterns. Arch Int Pharmacodyn Ther. 1986; 280(2 Suppl):50-61. View

20.

Mulsch A, Busse R, Liebau S, Forstermann U . LY 83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase. J Pharmacol Exp Ther. 1988; 247(1):283-8. View