Aronica E, Casabona G, Genazzani A A, Catania M V, Contestabile A, Virgili M, Nicoletti F
Institute of Pharmacology, University of Catania, School of Medicine, Italy.
Brain Res. 1992 Jul 17;586(1):72-7. doi: 10.1016/0006-8993(92)91373-m.
Melittin, a potent activator of phospholipase A2, enhanced both spontaneous and depolarization-induced release of D-[3H]aspartate in primary cultures of cerebellar granule cells. The action of melittin was concentration-dependent (EC50 value = 300 ng/ml) and did not require the presence of extracellular Ca2+. Melittin also stimulated the release of glutamate and aspartate, in addition to other endogenous amino acids (taurine, alanine and gamma-aminobutyric acid). These effects were accompanied by an enhanced influx of 45Ca2+, which was in part mediated by the activation of excitatory amino acid receptors by endogenous agonists. Low concentrations of melittin (50 ng/ml) potentiated the efficacy of AMPA in stimulating 45Ca2+ influx without affecting stimulation by kainate or by glutamate added in the absence of extracellular Mg2+ (a condition that favors the activation of NMDA receptors). These results indicate that activation of phospholipase A2 evokes both an enhanced glutamate release and an increased sensitivity of AMPA receptors, two events that may support synaptic facilitation and LTP formation.
蜂毒肽是磷脂酶A2的一种强效激活剂，它能增强小脑颗粒细胞原代培养物中D-[3H]天冬氨酸的自发释放和去极化诱导释放。蜂毒肽的作用呈浓度依赖性（半数有效浓度值=300纳克/毫升），且不需要细胞外钙离子的存在。除了其他内源性氨基酸（牛磺酸、丙氨酸和γ-氨基丁酸）外，蜂毒肽还能刺激谷氨酸和天冬氨酸的释放。这些效应伴随着45Ca2+内流的增加，这部分是由内源性激动剂对兴奋性氨基酸受体的激活介导的。低浓度的蜂毒肽（50纳克/毫升）增强了AMPA刺激45Ca2+内流的效力，而不影响海人藻酸或在无细胞外镁离子（有利于NMDA受体激活的条件）的情况下添加的谷氨酸的刺激作用。这些结果表明，磷脂酶A2的激活既会引起谷氨酸释放增强，也会导致AMPA受体敏感性增加，这两个事件可能有助于突触易化和长时程增强的形成。
