title: Signaling pathways in the nitric oxide and iron-induced dopamine release in the striatum of freely moving rats: role of extracellular Ca2+ and L-type Ca2+ channels.
abstract: We showed previously that exogenous iron potentiated nitric oxide (NO) donor-induced release of striatal dopamine (DA) in freely moving rats, using microdialysis. In this study, the increase in dialysate DA induced by intrastriatal infusion of the NO-donor 3-morpholinosydnonimine (SIN-1, 1.0 mM for 180 min) was scarcely affected by Ca2+ omission. N-methyl-d-glucamine dithiocarbamate (MGD) is a thiol compound whose NO trapping activity is potentiated by iron(II). Intrastriatal co-infusion of MGD either alone or associated with iron(II), however, potentiated SIN-1-induced increases in dialysate DA. In contrast, co-infusion of the NO trapper 4-(carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO) significantly attenuated the increase in dialysate DA induced by SIN-1 (5.0 mM for 180 min). SIN-1+MGD+iron(II)-induced increases in dialysate DA were inhibited by Ca2+ omission or co-infusion of either deferoxamine or the L-type (Ca(v) 1.1-1.3) Ca2+ channel inhibitor nifedipine; in contrast, the increase was scarcely affected by co-infusion of the N-type (Ca(v) 2.2) Ca2+ channel inhibitor omega-conotoxin GVIA. These results demonstrate that exogenous NO-induced release of striatal DA is independent on extracellular Ca2+; however, in presence of the NO trapper MGD, NO may preferentially react with either endogenous or exogenous iron to form a complex which releases striatal DA with an extracellular Ca2+-dependent and nifedipine-sensitive mechanism.
authors.affiliation: Department of Pharmacology, University of Sassari, viale S.Pietro 43B, 07100 Sassari, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Rocchitta
authors.forename: Rossana
authors.initials: R
authors.lastname: Migheli
authors.forename: Maria P
authors.initials: MP
authors.lastname: Mura
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.forename: Bianca
authors.initials: B
authors.lastname: Marchetti
authors.forename: Egidio
authors.initials: E
authors.lastname: Miele
authors.forename: Maria S
authors.initials: MS
authors.lastname: Desole
authors.forename: Maddalena
authors.initials: M
authors.lastname: Miele
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Serra
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009068:Movement / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000031:analogs & derivatives / Q000494:pharmacology; D013113:Spin Labels; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013859:Thiocarbamates / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology
chemical_list: D001565:Benzoates; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007093:Imidazoles; D007502:Iron Chelating Agents; D020030:Nitric Oxide Donors; D013113:Spin Labels; D013859:Thiocarbamates; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D013012:Sorbitol; C041262:N-methyl-D-glucamine dithiocarbamate; D007501:Iron; D002118:Calcium; D004298:Dopamine