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

Brain Res. 2005 Jun 14;1047(1):18-29. doi: 10.1016/j.brainres.2005.04.008.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Imidazoles / pharmacology
  • Iron / metabolism*
  • Iron / pharmacology
  • Iron Chelating Agents / pharmacology
  • Male
  • Microdialysis
  • Movement / physiology
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Wistar
  • Sorbitol / analogs & derivatives
  • Sorbitol / pharmacology
  • Spin Labels
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Thiocarbamates / pharmacology
  • Wakefulness / physiology

Substances

  • Benzoates
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Imidazoles
  • Iron Chelating Agents
  • Nitric Oxide Donors
  • Spin Labels
  • Thiocarbamates
  • 1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole
  • Nitric Oxide
  • Sorbitol
  • N-methyl-D-glucamine dithiocarbamate
  • Iron
  • Calcium
  • Dopamine