Sara V R, Carlsson-Skwirut C, Bergman T, Jörnvall H, Roberts P J, Crawford M, Håkansson L N, Civalero I, Nordberg A
Karolinska Institute's Department of Pathology, Karolinska Hospital, Stockholm, Sweden.
Biochem Biophys Res Commun. 1989 Dec 15;165(2):766-71. doi: 10.1016/s0006-291x(89)80032-4.
A truncated form of IGF-1 which lacks the aminoterminal tripeptide Gly-Pro-Glu (GPE) is found in human brain. It was proposed that GPE may result from neural specific processing and also have a function within the CNS. GPE was synthesized and shown to inhibit glutamate binding to the N-methyl-D-aspartate (NMDA) receptor. Whilst the carboxyterminal glutamate was necessary for NMDA receptor binding, the aminoterminal glycine potentiated receptor crossreaction. Furthermore, GPE had a potent stimulatory effect on the potassium induced release of acetylcholine from rat cortical slices. A less potent stimulation of dopamine release from striatum was also observed. The specific competitive NMDA receptor antagonist, (+/-)2-amino-7-phosphonoheptanoate (AP7), inhibited the action of GPE on dopamine but not on acetylcholine release. These studies have identified GPE as a novel neuroactive peptide with a potent action on acetylcholine release and support the general concept that the proteolytic products of the IGF-1 precursor play a role in the regulation of brain function.
在人类大脑中发现了一种截短形式的胰岛素样生长因子-1（IGF-1），它缺少氨基末端三肽甘氨酸-脯氨酸-谷氨酸（GPE）。有人提出，GPE可能是神经特异性加工的产物，并且在中枢神经系统中也具有功能。已合成GPE，并证明它能抑制谷氨酸与N-甲基-D-天冬氨酸（NMDA）受体的结合。虽然羧基末端谷氨酸对于NMDA受体结合是必需的，但氨基末端甘氨酸能增强受体交叉反应。此外，GPE对钾离子诱导的大鼠皮层切片乙酰胆碱释放具有强烈的刺激作用。还观察到对纹状体多巴胺释放有较弱的刺激作用。特异性竞争性NMDA受体拮抗剂（±）2-氨基-7-膦酰庚酸（AP7）可抑制GPE对多巴胺释放的作用，但不影响其对乙酰胆碱释放的作用。这些研究已将GPE确定为一种对乙酰胆碱释放具有强大作用的新型神经活性肽，并支持IGF-1前体的蛋白水解产物在脑功能调节中起作用这一普遍概念。
