Rodríguez-Moreno A, Lerma J
Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Neuron. 1998 Jun;20(6):1211-8. doi: 10.1016/s0896-6273(00)80501-2.
The mechanism through which kainate receptors downregulate the release of GABA in the hippocampus is not known. We have found that the action of kainate on the hippocampal inhibitory postsynaptic current (IPSC) is mediated by a metabotropic process that is sensitive to Pertussis toxin (PTx) and independent of ion channel current. The downregulation of GABA IPSCs by kainate was also prevented in a dose-dependent manner by calphostin C, a specific inhibitor of PKC, and the inhibition of phospholipase C (PLC) drastically reduced the action of kainate. The effect of kainate was completely occluded by phorbol esters and by increasing extracellular Ca2+ but remained unaltered after inhibition or activation of protein kinase A (PKA). These results demonstrate that the activation of kainate receptors triggers a second messenger cascade, which results in the stimulation of PKC, and therefore document a metabotropic action of kainate receptors, which results in the inhibition of GABA release.
红藻氨酸受体下调海马体中γ-氨基丁酸（GABA）释放的机制尚不清楚。我们发现，红藻氨酸对海马体抑制性突触后电流（IPSC）的作用是由一种对百日咳毒素（PTx）敏感且独立于离子通道电流的代谢型过程介导的。红藻氨酸对GABA IPSC的下调也被PKC的特异性抑制剂钙磷蛋白C以剂量依赖性方式阻止，并且磷脂酶C（PLC）的抑制显著降低了红藻氨酸的作用。佛波酯和增加细胞外Ca2+完全阻断了红藻氨酸的作用，但在蛋白激酶A（PKA）抑制或激活后保持不变。这些结果表明，红藻氨酸受体的激活触发了第二信使级联反应，导致PKC的刺激，因此证明了红藻氨酸受体的代谢型作用，其导致GABA释放的抑制。
