Serra, Pier Andrea and Esposito, Giovanni and Delogu, Maria Rosaria and Migheli, Rossana and Rocchitta, Gaia Giovanna Maria and Miele, Egidio and Desole, Maria Speranza and Miele, Maddalena (2001) Analysis of S-nitroso-N-acetylpenicillamine effects on dopamine release in the striatum of freely moving rats: role of endogenous ascorbic acid and oxidative stress. British Journal of Pharmacology, Vol. 132 (4), p. 941-949. eISSN 1476-5381. Article.
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1.We showed previously that interaction between NO and iron(II), both released following decomposition of sodium nitroprusside (SNP), accounted for the late SNP-induced dopamine (DA) increase in dialysates from the striatum of freely moving rats.
2.In this study, intrastriatal infusion of the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) (0.2mM for 180min) induced a moderate increase in dialysate DA and decreases in ascorbic acid dialysate concentrations; in contrast, SNAP 1mM infusion induced a long-lasting decrease in both DA and ascorbic acid dialysate concentrations. 3-Methoxy-tyramine (3-MT), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and uric acid levels were unaffected.
3.Co-infusion of ferrous sulphate [iron(II), 1mM for 40min] with SNAP either 1 or 0.2mM (for 180min), produced a significant increase in both DA and 3-MT dialysate concentrations, but it did not affect decreases in dialysate ascorbic acid levels. All other dialysate neurochemicals were unaffected.
4.Co-infusion of ascorbic acid (0.1mM) with SNAP (1mM) for 180min did not modify SNAP-induced decreases in dialysate DA levels. In contrast, co-infusion of uric acid (1mM) reversed SNAP-induced decreases in dialysate DA; co-infusion of a superoxide dismutase mimetic delayed SNAP-induced DA decreases for a short period, while co-infusion of the antioxidant N-acetylcysteine (NAC, 0.1mM) significantly increased dialysate DA.
5.The results of this study show that SNAP induces concentration-related changes in DA dialysate levels. At higher concentrations, SNAP induces non-enzymatic DA oxidation, which is inhibited by uric acid and NAC; ascorbic acid failed to protect dialysate DA from oxidation, probably owing to its promoting effect on SNAP decomposition; exogenous iron(II) may react with NO generated from SNAP decomposition, with a consequent increase in dialysate DA and 3-MT, therefore mimicking SNP effects on striatal DA release.
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