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一项关于一氧化氮和铁在3-吗啉代西多胺诱导的自由活动大鼠纹状体多巴胺释放增加中作用的研究。

A study on the role of nitric oxide and iron in 3-morpholino-sydnonimine-induced increases in dopamine release in the striatum of freely moving rats.

作者信息

Serra P A, Rocchitta G, Esposito G, Delogu M R, Migheli R, Miele E, Desole M S, Miele M

机构信息

Department of Pharmacology, University of Sassari, viale S. Pietro 43B, 07100 Sassari, Italy.

出版信息

Br J Pharmacol. 2001 Sep;134(2):275-82. doi: 10.1038/sj.bjp.0704232.

Abstract
  1. We showed previously that interaction between NO and iron (II), both released following the decomposition of sodium nitroprusside (SNP), accounted for the late SNP-induced dopamine (DA) increase in dialysates from the striatum of freely moving rats; in addition, we showed that co-infusion of iron (II) with the NO-donor S-nitroso-N-acetylpenicillamine mimicked SNP effects on striatal DA release. 2. In the present study, intrastriatal co-infusion of iron (II) (given as FeSO(4), 1 mM for 40 min) with the NO-donor and potential peroxynitrite generator 3-morpholinosydnonimine (SIN-1) (0.2, 0.5, 1.0 or 5.0 mM for 180 min), potentiated the SIN-1-induced increase in DA concentration in dialysates from the striatum of freely moving rats. Neither alone nor associated with iron (II) did SIN-1 induce changes in dialysate ascorbic acid or uric acid concentrations. 3. Neither co-infusion of a superoxide dismutase mimetic nor uric acid affected SIN-1-induced increases in dialysate DA concentration. 4. Infusion of the iron chelator deferoxamine (0.2 mM for 180 min) decreased dialysate DA and attenuated SIN-1-induced increases in dialysate DA concentrations. 5. These results suggest that iron plays a key role in SIN-1-induced release of striatal DA and do not support any role for either peroxynitrite or superoxide anion in SIN-1-induced release of striatal DA.
摘要
  1. 我们之前表明,硝普钠(SNP)分解后释放的一氧化氮(NO)与铁(II)之间的相互作用,是SNP诱导自由活动大鼠纹状体透析液中多巴胺(DA)后期增加的原因;此外,我们还表明,铁(II)与NO供体S-亚硝基-N-乙酰青霉胺共同输注可模拟SNP对纹状体DA释放的影响。2. 在本研究中,将铁(II)(以FeSO₄形式,1 mM,持续40分钟)与NO供体及潜在的过氧亚硝酸盐生成剂3-吗啉代-sydnonimine(SIN-1)(0.2、0.5、1.0或5.0 mM,持续180分钟)进行纹状体内共同输注,增强了SIN-1诱导的自由活动大鼠纹状体透析液中DA浓度的增加。单独使用SIN-1或与铁(II)联合使用时,均未引起透析液中抗坏血酸或尿酸浓度的变化。3. 超氧化物歧化酶模拟物或尿酸的共同输注均未影响SIN-1诱导的透析液DA浓度增加。4. 输注铁螯合剂去铁胺(0.2 mM,持续180分钟)可降低透析液中DA的含量,并减弱SIN-1诱导的透析液DA浓度增加。5. 这些结果表明,铁在SIN-1诱导的纹状体DA释放中起关键作用,并不支持过氧亚硝酸盐或超氧阴离子在SIN-1诱导的纹状体DA释放中起任何作用。

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