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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

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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DOI: 10.1038/sj.bjp.0703887

Abstract

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.

Item Type:Article
ID Code:5339
Status:Published
Refereed:Yes
Uncontrolled Keywords:NO-donor SNAP, dopamine, in vivo release, ascorbic acid, iron, microdialysis, rat striatum
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
Publisher:Macmillan
eISSN:1476-5381
Deposited On:21 Jan 2011 17:34

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