Transduction of a protein kinase C-generated signal into the long-lasting facilitation of glutamate release.
Transduction of a protein kinase C-generated signal into the long-lasting facilitation of glutamate release.
复制标题
将蛋白激酶 C 生成的信号转导为持久促进谷氨酸释放。
DOI：
10.1002/hipo.450030212
复制
发表时间：
1993
期刊：
影响因子：
3.5
通讯作者：
Zetts,DA
中科院分区：
文献类型：
--
作者：
Terrian,DM;Ways,DK;Gannon,RL;Zetts,DA
本研究调查了 4β-佛波醇 12, 13-二丁酸酯 (PDBu) 对 K+ 诱发的内源性谷氨酸和强啡肽 B 样免疫反应性从富含海马苔藓纤维突触体的亚细胞部分 (P3) 释放的延迟和持续影响。结果表明，使用豚鼠海马作为起始组织获得的 P3 级分中存在蛋白激酶 C (PKC) 的 α、β、γ、ε 和 zeta 亚型。当富含苔藓纤维的突触体与 PDBu 预孵育 15 分钟并用不含 PDBu 的培养基广泛洗涤时，K+ 诱发的谷氨酸释放会选择性增强。在此条件下观察到的谷氨酸释放的持续增强不会被蛋白激酶抑制剂星形孢菌素逆转，并且对急性再次暴露于 PDBu 的增强作用不敏感。在 PDBu (10 μM) 处理的最初 15 分钟内，PKC 的总体含量和活性没有显着改变。更长时间的 PDBu 预处理改变了 PKC 的底物特异性，并降低了所有 PKC 同工型的含量，但没有逆转在 PDBu 存在下预孵育后谷氨酸释放的促进作用。结论是，PKC 的持续激活增强了海马苔藓纤维丰富的突触体中 K+ 诱发的谷氨酸释放，并且一旦建立，这种突触前促进作用将通过一个不再直接依赖于持续的 PKC 磷酸转移酶活性的过程来维持。
The present study investigated the delayed and persistent effects of 4β‐phorbol 12, 13‐dibutyrate (PDBu) on the K+‐evoked release of endogenous glutamate and dynorphin B‐like immunoreactivity from a subcellular fraction (P3) that is enriched in hippocampal mossy fiber synaptosomes. It is demonstrated that the alpha, beta, gamma, epsilon, and zeta isoforms of protein kinase C (PKC) are present in the P3fraction obtained using the guinea pig hippocampus as starting tissue. The K+‐evoked release of glutamate was found to be selectively enhanced when mossy fiber‐enriched synaptosomes were preincubated with PDBu for 15 minutes and extensively washed with a PDBu‐free medium. The persistent enhancement of glutamate release observed under this condition was not reversed by the protein kinase inhibitor staurosporine and was desensitized to the potentiating effects of an acute reexposure to PDBu. The overall content and activity of PKC was not substantially altered during the initial 15 minutes of treatment with PDBu (10 μM). More prolonged pretreatments with PDBu altered the substrate specificity of PKC and decreased the content of all PKC isoforms, but did not reverse the facilitation of glutamate release that followed preincubation in the presence of PDBu. It is concluded that the persistent activation of PKC enhances K+‐evoked glutamate release from hippocampal mossy fiber‐enriched synaptosomes and that, once established, this presynaptic facilitation is sustained by a process that is no longer directly dependent on continued PKC phosphotransferase activity.