INFLUENCE OF SUPEROXIDE-DISMUTASE INHIBITION ON THE DISCRIMINATION BETWEEN NO AND THE NITRERGIC NEUROTRANSMITTER IN THE RAT GASTRIC FUNDUS

1 The influence of diethyldithiocarbamate (DETCA), that irreversibly i nhibits Cu/Zn-containing superoxide dismutase, on the inability of 6-a nilino-5,s-quinolinedione (LY83583), hypoxanthine/xanthine oxidase, hy droquinone and hydroxocobalamin to reduce electrically-induced NANC re laxations in the rat gastric fundus was investigated. 2 Longitudinal m uscle strips of the rat gastric fundus were mounted for auxotonic reco rding in the presence of atropine and guanethidine and tone was raised by administration of prostaglandin F-2 alpha. DETCA (3 x 10(-3) M) sl ightly reduced the short-lasting relaxations induced by 10(-5) M exoge nous 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 (3x10(-5)-3x10(-3) M) concentration-dependen tly potentiated the inhibitory effect of LY83583 upon the electrically -induced relaxations, although this was less pronounced than the inhib ition of the NO-induced relaxations. The inhibition of the electricall y-induced non-adrenergic noncholinergic (NANC) relaxations was not rev ersed by SOD while that of the NO-induced relaxations was partially re versed. 4 The inhibitory effect of hypoxanthine/xanthine oxidase, hydr oquinone and hydroxocobalamin on the electrically-induced NANC relaxat ions in the presence of DETCA (3 x 10(-3) M) was not different from th e inhibitory effect of DETCA alone. 5 It was concluded that the differ entiating effect of LY83583 between exogenous NO and the endogenous ni trergic neurotransmitter is partially related to protection of the end ogenous nitrergic neurotransmitter by high levels of intracellular sup eroxide dismutase. This mechanism does not hold for hydroquinone and h ydroxocobalamin, as they still discriminate between exogenous NO and t he endogenous nitrergic neurotransmitter in the presence of DETCA. The possibility that the endogenous nitrergic neurotransmitter is not fre e NO in the rat gastric fundus therefore remains open.