title: 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.
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) (0.2 mM for 180 min) induced a moderate increase in dialysate DA and decreases in ascorbic acid dialysate concentrations; in contrast, SNAP 1 mM 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), 1 mM for 40 min] with SNAP either 1 or 0.2 mM (for 180 min), 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 (0.1 mM) with SNAP (1 mM) for 180 min did not modify SNAP-induced decreases in dialysate DA levels. In contrast, co-infusion of uric acid (1 mM) 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, 0.1 mM) 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.
authors.affiliation: Department of Pharmacology, University of Sassari, viale S.Pietro 43B, 07100 Sassari, Italy.
authors.forename: P A
authors.initials: PA
authors.lastname: Serra
authors.forename: G
authors.initials: G
authors.lastname: Esposito
authors.forename: M R
authors.initials: MR
authors.lastname: Delogu
authors.forename: R
authors.initials: R
authors.lastname: Migheli
authors.forename: G
authors.initials: G
authors.lastname: Rocchitta
authors.forename: E
authors.initials: E
authors.lastname: Miele
authors.forename: M S
authors.initials: MS
authors.lastname: Desole
authors.forename: M
authors.initials: M
authors.lastname: Miele
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D018384:Oxidative Stress; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine
chemical_list: D020030:Nitric Oxide Donors; D026423:S-Nitroso-N-Acetylpenicillamine; D007501:Iron; D010396:Penicillamine; D001205:Ascorbic Acid; D004298:Dopamine; D000111:Acetylcysteine