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), the aminoterminal tripeptide of IGF-1, on the potassium (35 mM K+) stimulated release of acetyl-choline (ACh) from rat cortical slices were investigated. GPE significantly increased the release of ACh in the dose range of 10(-10)-10(-6) M, while IGF-1 significantly enhanced the release 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 available to the brain slices. The possible underlying mechanisms of action of GPE in the cholinergic synapse were investigated. GPE (10(-5) M) significantly (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 interact with the choline uptake sites ([H-3]hemicholinium binding) or the muscarinic ([H-3]QNB) receptor binding sites in rat cortex. The mechanism of action behind GPEs enhancement of cholinergic transmission is therefore still unknown.