We showed previously, using in vitro microdialysis, that activation of the nitric oxide (NO)/cyclic GMP pathway was the underlying mechanism of exogenous NO-induced dopamine (DA) secretion from PC12 cells. In this study, infusion of the potential peroxynitrite generator 3-morpholinosydnonimine (SIN-1, 1.0 mM for 60 min) induced a long-lasting decrease in dialysate DA+3-methoxytyramine (3-MT) in dialysates from PC12 cell suspensions. Ascorbic acid (0.2 mM) co-infusion allowed SIN-1 to increase dialysate DA+3-MT. SIN-1+ascorbic acid effects were abolished by Ca2+ omission. Infusion of high K+ (75 mM) induced a 2.5-fold increase in dialysate DA+3-MT. The increase was inhibited by SIN-1 co-infusion. Conversely, co-infusion of ascorbic acid (0.2 mM) with SIN-1+high K+ resulted in a 3.5 fold increase in dialysate DA+3-MT. The L-type Ca2+ channel inhibitor nifedipine selectively inhibited the DA+3-MT increase pertaining to high K+, while the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]-oxadiazolo[4,3]quinoxalin-1-one selectively inhibited the increase pertaining to SIN-1 effects. These results suggest that activation of the NO/sGC/cyclic GMP pathway is the underlying mechanism of extracellular Ca2+-dependent effects of SIN-1 on DA secretion from PC12 cells. Extracellular Ca2+ entry occurs through nifedipine-insensitive channels. Ascorbic acid is a key determinant in modulating the distinct profiles of SIN-1 effects.
Role of the nitric oxide/cyclic GMP pathway and ascorbic acid in 3-morpholinosydnonimine (SIN-1)-induced increases in dopamine secretion from PC12 cells. A microdialysis in vitro study / Serra, Pier Andrea; Migheli, Rossana; Rocchitta, Gaia Giovanna Maria; Taras, Mg; Mura, Mp; Delogu, Mr; Esposito, G; Desole, Maria Speranza; Miele, E; Miele, M.. - In: NEUROSCIENCE LETTERS. - ISSN 0304-3940. - 353:1(2003), pp. 5-8.
Role of the nitric oxide/cyclic GMP pathway and ascorbic acid in 3-morpholinosydnonimine (SIN-1)-induced increases in dopamine secretion from PC12 cells. A microdialysis in vitro study
SERRA, Pier Andrea;MIGHELI, Rossana;ROCCHITTA, Gaia Giovanna Maria;DESOLE, Maria Speranza;
2003-01-01
Abstract
We showed previously, using in vitro microdialysis, that activation of the nitric oxide (NO)/cyclic GMP pathway was the underlying mechanism of exogenous NO-induced dopamine (DA) secretion from PC12 cells. In this study, infusion of the potential peroxynitrite generator 3-morpholinosydnonimine (SIN-1, 1.0 mM for 60 min) induced a long-lasting decrease in dialysate DA+3-methoxytyramine (3-MT) in dialysates from PC12 cell suspensions. Ascorbic acid (0.2 mM) co-infusion allowed SIN-1 to increase dialysate DA+3-MT. SIN-1+ascorbic acid effects were abolished by Ca2+ omission. Infusion of high K+ (75 mM) induced a 2.5-fold increase in dialysate DA+3-MT. The increase was inhibited by SIN-1 co-infusion. Conversely, co-infusion of ascorbic acid (0.2 mM) with SIN-1+high K+ resulted in a 3.5 fold increase in dialysate DA+3-MT. The L-type Ca2+ channel inhibitor nifedipine selectively inhibited the DA+3-MT increase pertaining to high K+, while the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]-oxadiazolo[4,3]quinoxalin-1-one selectively inhibited the increase pertaining to SIN-1 effects. These results suggest that activation of the NO/sGC/cyclic GMP pathway is the underlying mechanism of extracellular Ca2+-dependent effects of SIN-1 on DA secretion from PC12 cells. Extracellular Ca2+ entry occurs through nifedipine-insensitive channels. Ascorbic acid is a key determinant in modulating the distinct profiles of SIN-1 effects.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.