West A R, Galloway M P
Department of Neuroscience, University of Pittsburgh, PA 15260, USA.
Neurochem Int. 1998 Dec;33(6):493-501. doi: 10.1016/s0197-0186(98)00054-0.
Previous studies investigating the calcium-dependency of nitric oxide-facilitated striatal dopamine efflux have produced conflicting results. In the current study, we have investigated the role of extracellular calcium in nitric oxide and potassium chloride-evoked striatal dopamine efflux in vivo using microdialysis. Dialysis probes were implanted in the anterior dorsal striatum of chloral hydrate-anesthetized rats. Intrastriatal infusion (20 min fraction) of the nitric oxide generators sodium nitroprusside (200 microM, 500 microM, or 1 mM) and 3-morpholinosydnonimine (1 mM) increased extracellular dopamine levels. The facilitatory effects of 3-morpholinosydnonimine and potassium chloride on dopamine efflux were attenuated following pretreatment (100 min) and co-infusion of calcium free artificial cerebral spinal fluid containing magnesium chloride. Local potassium chloride infusion (100 mM) administered alone elevated striatal dopamine efflux to a similar degree as potassium chloride (100 mM) delivered 60 min after 3-morpholinosydnonimine infusion. These results demonstrate that like potassium chloride, nitric oxide facilitates striatal dopamine efflux in vivo via a mechanism largely dependent on extracellular calcium. Also, as intrastriatal potassium chloride infusion evoked similar increases in extracellular dopamine levels in controls and subjects receiving pretreatment with the NO-generator 3-morpholinosydnonimine, it is unlikely that the functional integrity of DA nerve terminals is compromised via a neurotoxic disruption of plasma membrane potential following enhanced striatal NO production.
以往研究一氧化氮促进纹状体多巴胺外流的钙依赖性时，得出了相互矛盾的结果。在本研究中，我们使用微透析技术，研究了细胞外钙在体内一氧化氮和氯化钾诱发的纹状体多巴胺外流中的作用。将透析探针植入水合氯醛麻醉大鼠的前背侧纹状体。纹状体内注入（20分钟时间段）一氧化氮供体硝普钠（200微摩尔、500微摩尔或1毫摩尔）和3-吗啉代非那明（1毫摩尔）可提高细胞外多巴胺水平。在预处理（100分钟）并共同注入含氯化镁的无钙人工脑脊液后，3-吗啉代非那明和氯化钾对多巴胺外流的促进作用减弱。单独给予局部氯化钾注入（100毫摩尔），使纹状体多巴胺外流升高的程度与在注入3-吗啉代非那明60分钟后给予氯化钾（100毫摩尔）相似。这些结果表明，与氯化钾一样，一氧化氮在体内通过一种很大程度上依赖细胞外钙的机制促进纹状体多巴胺外流。此外，由于在对照组和接受一氧化氮供体3-吗啉代非那明预处理的受试者中，纹状体内注入氯化钾引起的细胞外多巴胺水平升高相似，因此在纹状体一氧化氮生成增加后，多巴胺神经末梢的功能完整性不太可能因质膜电位的神经毒性破坏而受损。
