DOPAMINE TRANSPORTER AND VESICULAR MONOAMINE TRANSPORTER

多巴胺转运蛋白（DAT）已被鉴定为 作为主要的大脑受体部位， 可卡因的奖励和欣快特性。欣快反应 可卡因的快速给药 而不是那些缓慢给药的人。前几 FYs，该分支的研究人员发现， 蛋白激酶C（PKC）调节多巴胺转运， 瞬时表达COS细胞。在本财年，我们遵循 先前的观察将DAT鉴定为磷蛋白， 确定了主要的丝氨酸磷酸受体位点， 磷酸氨基酸分析。基因定点突变体的研究 潜在的磷酸受体位点没有识别出单一的残基作为唯一的 绝佳的价钱这些数据增加了PKC激活增强 在多个丝氨酸的DAT磷酸化水平， 磷酸化是一种越来越强的候选机制， 多巴胺能系统的快速适应 可卡因引起的欣快感

The dopamine transporter (DAT) has been identified as the principal brain receptor site previoiusly correlated with the rewarding and euphoric properties of cocaine. Euphoric responses to rapid administration of cocaine can be much more prominent than those that follow slower rates of administration. In previous FYs, investigators in this Branch have found that activators of protein kinase C (PKC) modulate dopamine transport in transiently-expressing COS cells. In this FY, we have followed previous observations that identified DAT as a phosphoprotein, and identified predominant serine phosphoacceptor sites in phosphoamino acid analyses. Studies of site directed mutants in potential phosphoacceptor sites identify no single residue as a sole site. These data increase evidence that PKC activation enhances levels of DAT phosphorylation at multiple serines, and makes phosphorylation an increasingly-strong candidate mechanism for rapid adaptations in dopaminergic systems relevant to cocaine-induced euphoria.