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  • Identification of Gly-Pro-Glu (GPE), the aminoterminal tripeptide of insulin-like growth factor 1 which is truncated in brain, as a novel neuroactive peptide.

Identification of Gly-Pro-Glu (GPE), the aminoterminal tripeptide of insulin-like growth factor 1 which is truncated in brain, as a novel neuroactive peptide.

Biochemical and biophysical research communications (1989-12-15)
V R Sara, C Carlsson-Skwirut, T Bergman, H Jörnvall, P J Roberts, M Crawford, L N Håkansson, I Civalero, A Nordberg
RESUMEN

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.