A study on the role of nitric oxide and iron in 3-morpholino-sydnonimine-induced increases in dopamine release in the striatum of freely moving rats.
1. We showed previously that interaction between NO and iron (II), both released following the decomposition of sodium nitroprusside (SNP), accounted for the late SNP-induced dopamine (DA) increase in dialysates from the striatum of freely moving rats; in addition, we showed that co-infusion of iron (II) with the NO-donor S-nitroso-N-acetylpenicillamine mimicked SNP effects on striatal DA release. 2. In the present study, intrastriatal co-infusion of iron (II) (given as FeSO(4), 1 mM for 40 min) with the NO-donor and potential peroxynitrite generator 3-morpholinosydnonimine (SIN-1) (0.2, 0.5, 1.0 or 5.0 mM for 180 min), potentiated the SIN-1-induced increase in DA concentration in dialysates from the striatum of freely moving rats. Neither alone nor associated with iron (II) did SIN-1 induce changes in dialysate ascorbic acid or uric acid concentrations. 3. Neither co-infusion of a superoxide dismutase mimetic nor uric acid affected SIN-1-induced increases in dialysate DA concentration. 4. Infusion of the iron chelator deferoxamine (0.2 mM for 180 min) decreased dialysate DA and attenuated SIN-1-induced increases in dialysate DA concentrations. 5. These results suggest that iron plays a key role in SIN-1-induced release of striatal DA and do not support any role for either peroxynitrite or superoxide anion in SIN-1-induced release of striatal DA.
Serra
P A
PA
Department of Pharmacology, University of Sassari, viale S. Pietro 43B, 07100 Sassari, Italy.
Rocchitta
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G
Esposito
G
G
Delogu
M R
MR
Migheli
R
R
Miele
E
E
Desole
M S
MS
Miele
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D015314:Dialysis Solutions / Q000737:chemistry; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009068:Movement; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000378:metabolism / Q000494:pharmacology
D015314:Dialysis Solutions; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D020030:Nitric Oxide Donors; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D015102:3,4-Dihydroxyphenylacetic Acid; D014527:Uric Acid; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D007501:Iron; D003676:Deferoxamine; D001205:Ascorbic Acid; D004298:Dopamine; D000111:Acetylcysteine; D006719:Homovanillic Acid