Corticosteroids exert a dual role in eukaryotic cells through their action via (1) intracellular receptors (slow genomic responses), or (2) membrane-bound receptors (fast non-genomic responses). Highly vulnerable regions of the brain, like the hippocampus, express high amounts of corticosteroid receptors, yet their actions on ionic currents and neurotransmitters release are still undefined. Here, we investigated the effect of methylprednisolone (MP) on GABA and glutamate (Glu) release from isolated nerve terminals of the rat hippocampus. MP favored both spontaneous and depolarization-evoked [¹⁴C]Glu release from rat hippocampal nerve terminals, without affecting [³H]GABA outflow. Facilitation of [¹⁴C]Glu release by MP is mediated by a Na⁺-dependent Ca²⁺-independent non-genomic mechanism relying on the activation of membrane-bound glucocorticoid (GR) and mineralocorticoid (MR) receptors sensitive to their antagonists mifepristone and spironolactone, respectively. The involvement of Na⁺-dependent high-affinity EAAT transport reversal was inferred by blockage of MP-induced [¹⁴C]Glu release by DL-TBOA. Depolarization-evoked [³H]GABA release in the presence of MP was partially attenuated by the selective P2X7 receptor antagonist A-438079, but this compound did not affect the release of [¹⁴C]Glu. Data indicate that MP differentially affects GABA and glutamate release from rat hippocampal nerve terminals via fast non-genomic mechanisms putatively involving the activation of membrane-bound corticosteroid receptors. Facilitation of Glu release strengthen previous assumptions that MP may act as a cognitive enhancer in rats, while crosstalk with ATP-sensitive P2X7 receptors may promote a therapeutically desirable GABAergic inhibitory control during paroxysmal epileptic crisis that might be particularly relevant when extracellular Ca²⁺ levels decrease below the threshold required for transmitter release.

皮质类固醇通过其作用（1）胞内受体（缓慢的基因组反应）或（2）膜结合受体（快速的非基因组反应）在真核细胞中发挥双重作用。大脑的高度脆弱区域（如海马）表达大量的皮质类固醇受体，但它们对离子电流和神经递质释放的作用仍未确定。在这里，我们调查了甲基强的松龙（MP）对大鼠海马离体神经末梢GABA和谷氨酸（Glu）释放的影响。MP有利于大鼠海马神经末梢自发和去极化诱发的[ ¹⁴ C] Glu释放，而不影响[ ³ H] GABA的流出。MP促进[ ¹⁴ C] Glu的释放由Na ⁺介导依赖性Ca ²⁺依赖性非基因组机制分别依赖于对拮抗剂米非司酮和螺内酯敏感的膜结合糖皮质激素（GR）和盐皮质激素（MR）受体的激活。DL-TBOA阻滞了MP诱导的[ ¹⁴ C] Glu释放，从而推断了Na ⁺依赖性高亲和力EAAT转运的逆转。在MP存在下，去极化诱发的[ ³ H] GABA的释放被选择性P2X7受体拮抗剂A-438079所部分减弱，但该化合物并不影响[ ¹⁴ H] GABA的释放。C] Glu。数据表明，MP通过快速的非基因组机制推论涉及膜结合皮质类固醇受体的激活，从而差异性地影响GABA和谷氨酸从大鼠海马神经末梢的释放。促进Glu释放增强了以前的假设，即MP可能是大鼠的认知增强剂，而与ATP敏感的P2X7受体的串扰可能会促进阵发性癫痫危机中治疗上所需的GABA能抑制性控制，这可能在细胞外Ca ²⁺水平降低时尤其重要低于发射器释放所需的阈值。