Presynaptic inhibition by kainate receptors converges mechanistically with presynaptic inhibition by adenosine and GABAB receptors.
Presynaptic inhibition by kainate receptors converges mechanistically with presynaptic inhibition by adenosine and GABAB receptors.
复制标题
红藻氨酸受体的突触前抑制与腺苷和 GABAB 受体的突触前抑制在机制上是一致的。
DOI：
10.1016/j.neuropharm.2006.06.010
复制
发表时间：
2006
影响因子：
4.7
通讯作者：
Frerking,Matthew
中科院分区：
文献类型：
--
作者：
Partovi,Dara;Frerking,Matthew
红藻氨酸受体被广泛报道调节中枢神经系统中神经递质的释放，但所涉及的机制仍然存在争议。先前的研究已经发现，红藻氨酸受体激动剂ATPA选择性地激活含有GluK 5的红藻氨酸受体，抑制海马中Schaffer侧支突触的谷氨酸释放。在本研究中，我们提供的药理学证据表明，这种抑制作用是由含GluK 5的异聚体介导的，但与红藻氨酸受体激动剂domoate所引起的类似抑制作用不同。ATPA的抑制作用对GABAA、GABAB和腺苷受体的拮抗剂不敏感，并且也不受通过减少细胞外钙而降低释放概率的影响。然而，ATPA的作用被GABA受体的预先激活部分阻断，被腺苷受体的预先激活完全阻断，表明异聚体GluK 5红藻氨酸受体信号传导与GABA受体和腺苷受体的机械会聚。domoate的作用被腺苷和GABAB受体激动剂部分阻断，表明GluK 5缺乏的红藻氨酸受体信号传导与这些其他途径至少部分会聚。ATPA的抑制作用不被丝氨酸/苏氨酸蛋白激酶的抑制所阻断。这些结果表明，ATPA和domoate抑制谷氨酸释放的机制，收敛与经典的代谢型受体激动剂，虽然他们这样做，通过不同的受体。
Kainate receptors are widely reported to regulate the release of neurotransmitter in the CNS, but the mechanisms involved remain controversial. Previous studies have found that the kainate receptor agonist ATPA, which selectively activates GluK5-containing kainate receptors, depresses glutamate release at Schaffer-collateral synapses in the hippocampus. In the present study, we provide pharmacological evidence that this depressant effect is mediated by GluK5-containing heteromers, but is distinct from a similar depressant effect engaged by the kainate receptor agonist domoate. The depressant effect of ATPA is insensitive to antagonists for GABAA, GABAB, and adenosine receptors, and is also unaffected by lowering the release probability by reducing extracellular calcium. However, the effect of ATPA is partly occluded by prior activation of GABABreceptors and completely occluded by prior activation of adenosine receptors, suggesting a mechanistic convergence of heteromeric GluK5kainate receptor signaling with GABABreceptors and adenosine receptors. The effects of domoate are partially occluded by both adenosine and GABABreceptor agonists, indicating at least a partial convergence of GluK5-lacking kainate receptor signaling with these other pathways. The depressant effect of ATPA is not blocked by inhibition of serine/threonine protein kinases. These results suggest that ATPA and domoate inhibit glutamate release through mechanisms that converge with those of classical metabotropic receptor agonists, although they do so through different receptors.