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Role of the nitric oxide/cyclic GMP pathway and extracellular environment in the nitric oxide donor‐induced increase in dopamine secretion from PC12 cells: a microdialysis in vitro study
Author(s) -
Serra Pier Andrea,
Rocchitta Gaia,
Delogu Maria R.,
Migheli Rossana,
Taras Maria G.,
Mura Maria P.,
Esposito Giovanni,
Miele Egidio,
Desole Maria S.,
Miele Maddalena
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01947.x
Subject(s) - nitric oxide , microdialysis , snap , ascorbic acid , chemistry , extracellular , nifedipine , extracellular fluid , soluble guanylyl cyclase , sodium nitroprusside , medicine , endocrinology , pharmacology , calcium , biochemistry , cyclic gmp , computer graphics (images) , food science , organic chemistry , computer science
Abstract In vitro microdialysis was used to investigate the mechanism of nitric oxide (NO) donor‐induced changes in dopamine (DA) secretion from PC12 cells. Infusion of the NO‐donor S‐nitroso‐ N ‐acetylpenicillamine (SNAP, 1.0 m m ) induced a long‐lasting increase in DA and 3‐methoxytyramine (3‐MT) dialysate concentrations. SNAP‐induced increases were inhibited either by pre‐infusion of the soluble guanylate cyclase (sGC) inhibitor 1H‐[1,2,4] oxadiazolo[4,3]quinoxalin‐1‐one (ODQ, 0.1 m m ) or by Ca 2+ omission. Ca 2+ re‐introduction restored SNAP effects. SNAP‐induced increases in DA + 3‐MT were unaffected by co‐infusion of the l ‐type Ca 2+ channel inhibitor nifedipine. The NO‐donor (+/–)‐(E)‐4‐ethyl‐2‐[(E)‐hydroxyimino]‐5‐nitro‐3‐hexenamide (NOR‐3, 1.0 m m ) induced a short‐lasting decrease in dialysate DA + 3‐MT. Ascorbic acid (0.2 m m ) co‐infusion allowed NOR‐3 to increase dialysate DA + 3‐MT. ODQ pre‐infusion inhibited NOR‐3 + ascorbic acid‐induced DA + 3‐MT increases. Infusion of high K + (75 m m ) induced a 2.5‐fold increase in dialysate DA + 3‐MT. The increase was abolished by NOR‐3 co‐infusion. Conversely, co‐infusion of ascorbic acid (0.2 m m ) with NOR‐3 + high K + restored high K + effects. Co‐infusion of nifedipine inhibited high K + ‐induced DA + 3‐MT increases. These results suggest that activation of the NO/sGC/cyclic GMP pathway may be the underlying mechanism of extracellular Ca 2+ ‐dependent effects of exogenous NO on DA secretion from PC12 cells. Extracellular Ca 2+ entry may occur through nifedipine‐insensitive channels. NO effects and DA concentrations in dialysates largely depend on both the timing of NO generation and the extracellular environment in which NO is generated.