title: 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.
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 mm) 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 mm) or by Ca2+ omission. Ca2+ re-introduction restored SNAP effects. SNAP-induced increases in DA + 3-MT were unaffected by co-infusion of the l-type Ca2+ channel inhibitor nifedipine. The NO-donor (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3, 1.0 mm) induced a short-lasting decrease in dialysate DA + 3-MT. Ascorbic acid (0.2 mm) 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 mm) 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 mm) 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 Ca2+-dependent effects of exogenous NO on DA secretion from PC12 cells. Extracellular Ca2+ 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.
authors.affiliation: Department of Pharmacology, University of Sassari, Sassari, Italy.
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Serra
authors.forename: Gaia
authors.initials: G
authors.lastname: Rocchitta
authors.forename: Maria R
authors.initials: MR
authors.lastname: Delogu
authors.forename: Rossana
authors.initials: R
authors.lastname: Migheli
authors.forename: Maria G
authors.initials: MG
authors.lastname: Taras
authors.forename: Maria P
authors.initials: MP
authors.lastname: Mura
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
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
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002470:Cell Survival; D006152:Cyclic GMP / Q000378:metabolism*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism*; D006719:Homovanillic Acid / Q000032:analysis / Q000378:metabolism; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000188:drug therapy / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C061872:FK 409; D006152:Cyclic GMP; C001746:3-methoxytyramine; D001205:Ascorbic Acid; D011188:Potassium; D002118:Calcium; D004298:Dopamine; D006719:Homovanillic Acid