Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
Life Sci. 2011 Jul 18;89(3-4):137-40. doi: 10.1016/j.lfs.2011.05.021. Epub 2011 Jun 13.
Previous studies have shown that sphingosine 1-phosphate (S1P) stimulates glutamate release from hippocampal neurons. The present study was designed to understand the mechanism underlying S1P-induced spontaneous glutamate release from mossy fiber terminals in the hippocampus.
Slice patches were made from three different regions of neurons in rat hippocampal slices, and spontaneous α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor-mediated miniature excitatory postsynaptic currents (AMPA-mEPSCs) were monitored.
Inhibitors of sphingosine kinase such as dimethylsphingosine (DMS) and 2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole (HACPT), to suppress endogenous S1P production, significantly decreased the rate of spontaneous AMPA-mEPSCs elicited from CA3 pyramidal neurons, but not CA1 pyramidal neurons or dentate granular neurons. A similar decrease was also obtained with VPC23019, an inhibitor of S1P receptors, suramin, an inhibitor of S1P(3) receptor, U73122, an inhibitor of phospholipase C, or GF109203X, an inhibitor of protein kinase C.
The results of the present study show that endogenous S1P regulates spontaneous glutamate release in a restricted hippocampal area, i.e., the release from mossy fiber terminals, via S1P(3) receptors linked to G(q) protein. This may represent fresh insight into the regulatory mechanism of spontaneous transmitter release.
先前的研究表明，1-磷酸鞘氨醇（S1P）可刺激海马神经元释放谷氨酸。本研究旨在了解 S1P 诱导海马苔藓纤维末梢自发谷氨酸释放的机制。
从大鼠海马切片的 3 个不同神经元区域制作切片斑，并监测α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体介导的自发微小兴奋性突触后电流（AMPA-mEPSCs）。
抑制鞘氨醇激酶的抑制剂，如二甲基鞘氨醇（DMS）和 2-（对羟基苯胺基）-4-（对氯苯基）噻唑（HACPT），以抑制内源性 S1P 的产生，可显著降低 CA3 锥体神经元诱发的自发 AMPA-mEPSCs 的频率，但对 CA1 锥体神经元或齿状回颗粒神经元无影响。S1P 受体抑制剂 VPC23019、S1P（3）受体抑制剂苏拉明、PLC 抑制剂 U73122 或蛋白激酶 C 抑制剂 GF109203X 也可获得类似的降低。
本研究结果表明，内源性 S1P 通过与 G(q) 蛋白偶联的 S1P(3)受体调节特定海马区域（即苔藓纤维末梢）的自发谷氨酸释放，这可能为自发递质释放的调节机制提供新的见解。
