title: Sodium nitroprusside stimulates L-DOPA release from striatal tissue through nitric oxide and cGMP.
abstract: The effects of the nitric oxide (NO) donor, sodium nitroprusside, on L-DOPA and dopamine release from striatal tissue were evaluated using a static incubation system in which the striatal tissue released between three and six times more L-DOPA than DA, although the DA content was four times higher than that of L-DOPA. Sodium nitroprusside stimulated L-DOPA release in a time- and concentration-dependent (25, 50 and 100 microM) manner. This effect was not due to an increase in L-DOPA synthesis because sodium nitroprusside did not modify the tyrosine hydroxylase activity of striatal tissue. DA release was also stimulated by sodium nitroprusside but it required a higher concentration (500 microM) and longer incubation (60 min). Neither basal nor sodium nitroprusside-stimulated L-DOPA release was influenced by Ca(2+) deprivation (EGTA 5 mM) and/or the presence of nitrendipine (1 microM), a blocker Ca(2+) channel, in the incubation medium. However, cGMP (1 mM) increased L-DOPA release, and the soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ) (5 microM), partially blunted the stimulatory effect of sodium nitroprusside 100 microM. In addition, the presence of certain scavengers of free radicals, such as uric acid (300 microM) or melatonin (300 microM) but not of superoxide dismutase (1000 UI/ml) or salicylic acid (300 microM), completely blocked sodium nitroprusside (100 microM)-induced L-DOPA release. These results show that NO stimulates L-DOPA release from striatal tissue by an apparently Ca(2+)-independent mechanism, mediated by cGMP but also by peroxynitrite.
authors.affiliation: Department of Physiology, School of Medicine, University of La Laguna, La Cuesta, E-38320 Tenerife, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: Pedro
authors.initials: P
authors.lastname: Abreu
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; D009599:Nitroprusside; D014527:Uric Acid; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D007980:Levodopa; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D008550:Melatonin; D020156:Salicylic Acid