多巴胺自身受体通过抑制依赖cAMP的磷酸化调控TH活性

DOPAMINE AUTORECEPTORS REGULATE THE ACTIVITY OF TYROSINE HYDROXYLASE THROUGH THE INHIBITION OF cAMPDEPENDENT PHOSPHORYLATION

应用ＨＰＬＣ－ＥＣＤ法测定大鼠纹状体突触体ＴＨ的活性，研究ＤＡ自身受体介导的ＤＡ生物合成负反馈调控的机理。研究发现，ＡＣ激活剂ＦＳＫ和ＰＫＡ激活剂ｄｂｃＡＭＰ均以浓度依赖的方式激活突触体ＴＨ的活性，增加ｌ－ｄｐｏａ的生成。ＤＡ自身受体激动剂ＬＹ１７１５５５能抑制ＦＳＫ对ＴＨ的激活效应，但不影响ｄｂｃＡＭＰ对ＴＨ的激活。实验结果表明，ＤＡ自身受体介导的负反馈调控的机理是通过抑制依赖ｃＡＭＰ的ＰＫＡ对ＴＨ的磷酸化激活，其作用环节在于抑制ＡＣ，而不是对ＰＫＡ的直接抑制。

To search into the mechanism of the negative feedback regulation of dopamine (DA) biosynthesis mediated by DA autoreceptors, the activity of synaptosomal tyrosine hydroxylase (TH) from rat striatum was assayed by HPLC-ECD method. The results showed that both adenylate cyclase (AC) activator forskolin (FSK) and protein kinase A (PKA) activator dibutyryl cAMP (dbcAMP) stimulated synaptosomal TH activity in a concentrationdependent manner, and therefore increased the formation of 1-dopa. Moreover, DA autoreceptor agonist LY171555 could antagonize the activating effect of FSK on synaptosomal TH, but not that of dbcAMP. These results suggest that the negative feedback regulation on DA biosynthesis mediated by DA autoreceptors may be coupled with the inhibition of cAMp-dependent phosphorylation of TH through the inhibition of AC, but not of PKA.