Chittajallu R, Vignes M, Dev K K, Barnes J M, Collingridge G L, Henley J M
Department of Anatomy, School of Medical Sciences, University of Bristol, UK.
Nature. 1996 Jan 4;379(6560):78-81. doi: 10.1038/379078a0.
Most reported actions of kainate are mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors. Here we report that, unlike AMPA which stimulates, kainate elicits a dose-dependent decrease in L-glutamate release from rat hippocampal synaptosomes and also depresses glutamatergic synaptic transmission. Brief exposure to kainate inhibited Ca(2+)-dependent [3H]L-glutamate release by up to 80%. Inhibition was reversed by kainate antagonists but not by the AMPA-selective non-competitive antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466). A corresponding reversible kainate-evoked depression of NMDA (N-methyl-D-aspartate) receptor-mediated excitatory postsynaptic currents (e.p.s.cs) was observed when AMPA receptors were blocked by GYKI 52466. The synaptic depression was preceded by a brief period of enhanced release and a small inward current was also observed. The effects of kainate were unaffected by metabotropic glutamate (mGlu), GABAA, GABAB, glycine and adenosine receptor antagonists. These results indicate that glutamate release can be modulated directly by kainate autoreceptors.
大多数所报道的海人酸的作用是由AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体介导的。在此我们报告，与具有刺激作用的AMPA不同，海人酸会引起大鼠海马突触体中L-谷氨酸释放呈剂量依赖性减少，并且还会抑制谷氨酸能突触传递。短暂暴露于海人酸会使依赖Ca(2+)的[3H]L-谷氨酸释放最多抑制80%。海人酸拮抗剂可逆转这种抑制作用，但AMPA选择性非竞争性拮抗剂1-(4-氨基苯基)-4-甲基-7,8-亚甲基二氧基-5H-2,3-苯并二氮杂卓（GYKI 52466）则不能。当AMPA受体被GYKI 52466阻断时，观察到相应的、可逆转的海人酸诱发的NMDA（N-甲基-D-天冬氨酸）受体介导的兴奋性突触后电流（e.p.s.cs）抑制。突触抑制之前有一段短暂的释放增强期，并且还观察到一个小的内向电流。海人酸的作用不受代谢型谷氨酸（mGlu）、GABAA、GABAB、甘氨酸和腺苷受体拮抗剂的影响。这些结果表明，谷氨酸释放可被海人酸自身受体直接调节。
