EFFECTS OF IGF-1, TRUNCATED IGF-1 AND THE TRIPEPTIDE GLY-PRO-GLU ON ACETYLCHOLINE-RELEASE FROM PARIETAL CORTEX OF RAT-BRAIN

THE effects of intact IGF-1, truncated IGF-1 and Gly-Pro-Glu (GPE), th e aminoterminal tripeptide of IGF-1, on the potassium (35 mM K+) stimu lated release of acetyl-choline (ACh) from rat cortical slices were in vestigated. GPE significantly increased the release of ACh in the dose range of 10(-10)-10(-6) M, while IGF-1 significantly enhanced the rel ease of ACh only at 4 x 10(-8) M. The truncated form of IGF-1, lacking the tripeptide GPE, did not effect the release of ACh in rat cortex. Binding experiments also showed that truncated IGF-1 was less availabl e to the brain slices. The possible underlying mechanisms of action of GPE in the cholinergic synapse were investigated. GPE (10(-5) M) sign ificantly (40%) displaced [H-3]nicotine from its binding sites in rat cortex. In the concentration range of 10(-10)-10(-5) M, GPE did not in teract with the choline uptake sites ([H-3]hemicholinium binding) or t he muscarinic ([H-3]QNB) receptor binding sites in rat cortex. The mec hanism of action behind GPEs enhancement of cholinergic transmission i s therefore still unknown.