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

Gaia Rocchitta, Rossana Migheli, Maria P. Mura, Giuseppe Grella, Giovanni Esposito, Bianca Marchetti, Egidio Miele, Maria S. Desole, Maddalena Miele, Pier Andrea Serra

Research output: Contribution to journalArticle


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 Ca 2+ omission or co-infusion of either deferoxamine or the L-type (Cav 1.1-1.3) Ca2+ channel inhibitor nifedipine; in contrast, the increase was scarcely affected by co-infusion of the N-type (Cav 2.2) Ca2+ channel inhibitor ω-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 Ca 2+-dependent and nifedipine-sensitive mechanism.

Original languageEnglish
Pages (from-to)18-29
Number of pages12
JournalBrain Research
Issue number1
Publication statusPublished - Jun 14 2005



  • Calcium channels
  • Complex
  • Exogenous nitric oxide
  • Iron
  • Parkinson's disease
  • Striatal dopamine release

ASJC Scopus subject areas

  • Neuroscience(all)

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