Serra P A, Esposito G, Delogu M R, Migheli R, Rocchitta G, Grella G, Miele E, Miele M, Desole M S
Department of Pharmacology, University of Sassari, viale S. Pietro 43B, 07100 Sassari, Italy.
Br J Pharmacol. 2000 Oct;131(4):836-42. doi: 10.1038/sj.bjp.0703635.
The effects of intrastriatal infusion of 3-morpholinosydnonimine (SIN-1) or sodium nitroprusside (SNP) on dopamine (DA), 3-methoxytyramine (3-MT), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), L-dihydroxyphenylalanine (L-DOPA), ascorbic acid and uric acid concentrations in dialysates from the striatum of freely moving rats were evaluated using microdialysis. SIN-1 (1 mM) infusion for 180 min increased microdialysate DA and 3-MT concentrations, while L-DOPA, DOPCA+HVA, ascorbic acid and uric acid levels were unaffected. Co-infusion with ascorbic acid (0.1 mM) inhibited SIN-1-induced increases in DA and 3-MT dialysate concentration. SNP (1 mM) infusion for 180 min increased greatly the dialysate DA concentration to a peak (2950% of baseline) at the end of the infusion, while increases in 3-MT were negligible. In addition, SNP decreased ascorbic acid and L-DOPA but increased uric acid concentration in the dialysate. Co-infusion with deferoxamine (0.2 mM) inhibited the late SNP-induced increase in DA dialysate concentration, but did not affect the decrease in ascorbic acid and increase uric acid dialysate concentrations. SNP (1 mM) infusion for 20 min moderately increased uric acid, DA and 3-MT, but decreased L-DOPA levels in the dialysate. Ascorbic acid concentration increased at the end of SNP infusion. Co-infusion with ascorbic acid (0.1 mM) inhibited the SNP-induced increase in DA and 3-MT, but did not affect the decrease in L-DOPA and increase in uric acid dialysate concentrations. These results suggest that NO released from SIN-1 may account for the increase in the dialysate DA concentration. NO released following decomposition of SNP may account for the early increase in dialysate DA, while late changes in microdialysate composition following SNP may result from an interaction between NO and the ferrocyanide moiety of SNP. Exogenous ascorbic acid inhibits the effect of exogenous NO on DA release probably by scavenging NO, suggesting that endogenous ascorbic acid may modulate the NO control of DA release from 300 striatal dopaminergic terminals.
采用微透析技术评估向自由活动大鼠纹状体内注射3-吗啉代亚硝基胍（SIN-1）或硝普钠（SNP）对纹状体透析液中多巴胺（DA）、3-甲氧基酪胺（3-MT）、二羟基苯乙酸（DOPAC）、高香草酸（HVA）、L-二羟基苯丙氨酸（L-DOPA）、抗坏血酸和尿酸浓度的影响。注射1 mM SIN-1 180分钟可使透析液中DA和3-MT浓度升高，而L-DOPA、DOPCA+HVA、抗坏血酸和尿酸水平不受影响。与抗坏血酸（0.1 mM）共同注射可抑制SIN-1诱导的透析液中DA和3-MT浓度升高。注射1 mM SNP 180分钟可使透析液中DA浓度大幅升高，在注射结束时达到峰值（为基线的2950%），而3-MT的升高可忽略不计。此外，SNP可降低透析液中抗坏血酸和L-DOPA的浓度，但可升高尿酸浓度。与去铁胺（0.2 mM）共同注射可抑制SNP后期诱导的透析液中DA浓度升高，但不影响抗坏血酸浓度降低和尿酸透析液浓度升高。注射1 mM SNP 20分钟可适度升高尿酸、DA和3-MT，但可降低透析液中L-DOPA水平。在SNP注射结束时抗坏血酸浓度升高。与抗坏血酸（0.1 mM）共同注射可抑制SNP诱导的DA和3-MT升高，但不影响L-DOPA降低和尿酸透析液浓度升高。这些结果表明，SIN-1释放的NO可能是透析液中DA浓度升高的原因。SNP分解后释放的NO可能是透析液中DA早期升高的原因，而SNP后透析液成分的后期变化可能是由于NO与SNP的亚铁氰化物部分相互作用所致。外源性抗坏血酸可能通过清除NO来抑制外源性NO对DA释放的影响，这表明内源性抗坏血酸可能调节来自300个纹状体多巴胺能终末的NO对DA释放的控制。
