DOPAMINE TRANSPORTER I--REGULATION BY PHOSPHORYLATION

多巴胺转运蛋白（DAT）已被确定为主要的大脑 受体部位与奖赏和欣快特性最相关 可卡因。对快速服用可卡因的欣快反应可能是 比那些以较慢的速度 局在以前的财政年度，本分支的调查人员发现， 蛋白激酶C（PKC）激活剂调节多巴胺转运， 瞬时表达COS细胞（Eur. J. Pharmacol.，268，115 - 119）。 在 本财年，我们已经确定DAT为磷蛋白，有证据表明 表达细胞系中的快速磷酸化/去磷酸化循环 和脑突触体中。 磷酸化与 同时确定DAT Vmax值的功能降低 实验 这些数据增加了PKC激活增强 DAT磷酸化水平，并使磷酸化 快速适应的候选机制越来越强， 与可卡因诱导的欣快相关的多巴胺能系统。

The dopamine transporter (DAT) has been identified as the principal brain receptor site best 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 (Eur. J. Pharmacol., 268, 115-119). In this FY, we have identified the DAT as a phosphoprotein with evidence for rapid phosphorylation/dephosphorylation cycling in expressing cell lines and in brain synaptosomes. Phosphorylation displays many parallels to functional reductions in DAT Vmax values identified in parallel experiments. These data increase evidnece that PKC activation enhances levels of DAT phosphorylation, and makes phosphorylation an increasingly-strong candidate mechanism for rapid adaptations in dopaminergic systems relevant to cocaine-induced euphoria.