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。     

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

In order to explore the characteristics of l-stepholidine (SPD) activating the postsynaptic D₁ receptors,the effects of SPD on DARPP-32 phosphorylation in vivo with back-phosphorylation assay and on the postsynaptic D₁ 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,［³²P］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 D₁ receptor B_max was decreased from 385.0±26.1 to 319.7±20.1 fmol/mg protein.It is suggested that D₁ agonist action of SPD decreases the D₁ 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 D₁ receptor signal transduction in brain neurons.