title: Signalling pathways in the nitric oxide donor-induced dopamine release in the striatum of freely moving rats: evidence that exogenous nitric oxide promotes Ca2+ entry through store-operated channels.
abstract: We showed previously, using in vitro microdialysis, that the activation of the soluble guanylate cyclase (sGC)/cyclic GMP pathway was the underlying mechanism of the extracellular Ca(2+)-dependent effects of exogenous NO on dopamine (DA) secretion from PC12 cells. In this study, the co-infusion of the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3] quinoxalin-1-one (ODQ) failed to affect the NO donor 3-morpholinosydnonimine (SIN-1, 5.0 mM)-induced DA increase (sevenfold baseline) in dialysates from the striatum of freely moving rats. Ca(2+) omission from the perfusion fluid abolished baseline DA release but did not affect SIN-1-induced DA increases. The reintroduction of Ca(2+) in the perfusion fluid restored the baseline dialysate DA; however, when Ca(2+) reintroduction was associated with the infusion of either SIN-1 or the NO-donor S-nitrosoglutathione (SNOG), a sustained DA overflow was observed. DA overflow was selectively inhibited by the co-infusion of the store-operated channel blocker 2-aminoethoxydiphenyl borate. The chelation of intracellular Ca(2+) by co-infusing 1,2-bis (o-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM, 0.2 mM) greatly potentiated both SIN-1- and SNOG-induced increases in dialysate DA. BAPTA-AM-induced potentiation was inhibited by Ca(2+) omission. We conclude that the sGC/cyclic GMP pathway is not involved in the extracellular Ca(2+)-independent exogenous NO-induced striatal DA release; however, when intracellular Ca(2+) is either depleted (by Ca(2+) omission) or chelated (by BAPTA-AM co-infusion), exogenous NO does promote Ca(2+) entry, most likely through store-operated channels, with a consequent further increase in DA release.
authors.affiliation: Department of Pharmacology, University of Sassari, viale S.Pietro 43B, 07100 Sassari, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Rocchitta
authors.forename: Rossana
authors.initials: R
authors.lastname: Migheli
authors.forename: Maria P
authors.initials: MP
authors.lastname: Mura
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.forename: Maria S
authors.initials: MS
authors.lastname: Desole
authors.forename: Egidio
authors.initials: E
authors.lastname: Miele
authors.forename: Maddalena
authors.initials: M
authors.lastname: Miele
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Serra
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004563:Electrochemistry / Q000379:methods; D007839:Functional Laterality / Q000187:drug effects; D008297:Male; D017551:Microdialysis / Q000379:methods; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D001896:Boron Compounds; D002614:Chelating Agents; D020030:Nitric Oxide Donors; D011810:Quinoxalines; D009569:Nitric Oxide; D004533:Egtazic Acid; D026422:S-Nitrosoglutathione; C002385:linsidomine; D008981:Molsidomine; C109986:2-aminoethoxydiphenyl borate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D004298:Dopamine