Signaling pathways in the nitric oxide and iron-induced dopamine release in the striatum of freely moving rats: Role of extracellular Ca super(2) super(+) and L-type Ca super(2) super(+) channels

• Published in: Brain research Vol. 1047; no. 1; pp. 18 - 29
• Main Authors: Rocchitta, G, Migheli, R, Mura, M P, Grella, G, Esposito, G, Marchetti, B, Miele, E, Desole, MS, Miele, M, Serra, P A
• Format: Journal Article
• Language: English
• Published: 14.06.2005
• ISSN: 0006-8993
• DOI: 10.1016/j.brainres.2005.04.008

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 Ca super(2) super(+) 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 Ca super(2) super(+) omission or co-infusion of either deferoxamine or the L-type (Ca sub(v) 1.1-1.3) Ca super(2) super(+) channel inhibitor nifedipine; in contrast, the increase was scarcely affected by co-infusion of the N-type (Ca sub(v) 2.2) Ca super(2) super(+) channel inhibitor omega -conotoxin GVIA. These results demonstrate that exogenous NO-induced release of striatal DA is independent on extracellular Ca super(2) super(+); 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 Ca super(2) super(+)-dependent and nifedipine-sensitive mechanism.