左旋千金藤啶碱D1激动作用增加6—OHDA损毁大鼠的DARPP—32磷酸化效应

INCREASED PHOSPHORYLATION OF DARPP 32 BY D 1 AGONISTIC ACTION OF l STEPHOLIDINE IN THE 6 OHDA LESIONED RAT STRIATUM 

为了进一步阐明ＳＰＤ对大鼠纹状体突触后Ｄ１受体的激动作用特性，本文应用反磷酸化在体内测定及放射配体结合方法，分别观察ＳＰＤ对６ＯＨＤＡ损毁大鼠纹状体ＤＡＲＰＰ３２体内磷酸化作用及突触后Ｄ１受体密度的影响。结果表明：皮下给予ＳＰＤ（２０，４０ｍｇ／ｋｇ，２１ｄ），损毁侧纹状体ＤＡＲＰＰ３２体外［３２Ｐ］的掺入量较健侧下降５０％（Ｐ＜００１）。换言之，损毁侧纹状体内ＤＡＲＰＰ３２的磷酸化程度增加了。然而，ＳＰＤ使损毁导致Ｄ１受体上调的作用减弱（Ｂｍａｘ从３８５０±２６１ｆｍｏｌ／ｍｇ降至３１９７±２０１ｆｍｏｌ／ｍｇ水平）。因此，ＳＰＤ激动Ｄ１受体，使６ＯＨＤＡ损毁大鼠纹状体内ＤＡＲＰＰ３２磷酸化作用加强，而受体密度减少。这是ＳＰＤ调节脑内Ｄ１受体信号转导功能的重要机制。

In order to explore the characteristics of l stepholidine (SPD) activating the postsynaptic D 1 receptors, the effects of SPD on DARPP 32 phosphorylation in vivo with back phosphorylation assay and on the postsynaptic D 1 receptor densities with radioligand assay were observed in the striatum of 6 OHDA lesioned rat. The results showed that following subcutaneously administration of 20 or 40 mg/kg SPD for 21 d, [ 32 P]phosphate incorporation into the DARPP 32 protein in the denervated striatum showed a 50% reduction ( P <0 01) vs the intact striatum, indicating an increase of DARPP 32 phosphorylation in vivo in the denervated striatum. However, the D 1 receptor B max was decreased from 385 0±26 1 to 319 7±20 1 fmol/mg protein. It is suggested that D 1 agonist action of SPD decreases the D 1 receptor density but increases the phosphorylation of DARPP 32 in the striatum of 6 OHDA lesioned rat, which may be responsible for the regulation of D 1 receptor signal transduction in brain neurons.