D2-class dopamine receptor inhibition of NMDA currents in prefrontal cortical neurons is platelet-derived growth factor receptor-dependent
D2-class dopamine receptor inhibition of NMDA currents in prefrontal cortical neurons is platelet-derived growth factor receptor-dependent
复制标题
DOI：
10.1111/j.1471-4159.2006.04064.x
复制
发表时间：
2006-09-01
影响因子：
4.7
通讯作者：
MacDonald, John F.
中科院分区：
文献类型：
--
作者：
Beazely, Michael A.;Tong, Andrew;MacDonald, John F.
NMDA受体功能受G蛋白偶联受体和受体酪氨酸激酶的调节。在急性分离的大鼠海马神经元中，血小板衍生生长因子（PDGF）受体的直接激活或D-4多巴胺受体对PDGF受体的反式激活以磷脂酶C（PLC）依赖的方式抑制NMDA诱发的电流。我们进一步研究了D-2类多巴胺受体对离体大鼠前额叶皮层（PFC）NMDA诱发电流的调节能力。我们已经证明，类似于分离的海马神经元，应用PDGF-BB或quinpirole分离PFC神经元诱导缓慢发作和持久的抑制NMDA诱发的电流。然而，与海马神经元相反，PFC神经元中喹吡罗对NMDA诱发电流的抑制依赖于D-2/3，而不是D-4，多巴胺受体。在PFC切片中，应用PDGF-BB和喹吡罗诱导了PLC γ结合和激活位点Tyr 1021处PDGF受体的磷酸化。PDGF受体激酶抑制剂tyrphostin A9和D-2/3多巴胺受体拮抗剂雷氯必利可抑制喹吡罗诱导的Tyr 1021磷酸化。这些发现表明，喹吡罗治疗通过海马和PFC中的PDGF受体反式激活来抑制NMDAR信号传导，并且喹吡罗在这些区域中的作用分别由D-4和D-2/3多巴胺受体介导。
NMDA receptor function is modulated by both G-protein-coupled receptors and receptor tyrosine kinases. In acutely isolated rat hippocampal neurons, direct activation of the platelet-derived growth factor (PDGF) receptor or transactivation of the PDGF receptor by D-4 dopamine receptors inhibits NMDA-evoked currents in a phospholipase C (PLC)-dependent manner. We have investigated further the ability of D-2-class dopamine receptors to modulate NMDA-evoked currents in isolated rat prefrontal cortex (PFC). We have demonstrated that, similar to isolated hippocampal neurons, the application of PDGF-BB or quinpirole to isolated PFC neurons induces a slow-onset and long-lasting inhibition of NMDA-evoked currents. However, in contrast to hippocampal neurons, the inhibition of NMDA-evoked currents by quinpirole in PFC neurons is dependent upon D-2/3, rather than D-4, dopamine receptors. In PFC slices, application of both PDGF-BB and quinpirole induced a phosphorylation of the PDGF receptor at the PLC gamma binding and activation site, Tyr1021. The PDGF receptor kinase inhibitor, tyrphostin A9, and the D-2/3 dopamine receptor antagonist, raclopride, inhibited quinpirole-induced Tyr1021 phosphorylation. These finding suggest that quinpirole treatment inhibits NMDAR signaling via PDGF receptor transactivation in both the hippocampus and the PFC, and that the effects of quinpirole in these regions are mediated by D-4 and D-2/3 dopamine receptors, respectively.