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 acetylcholine (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 [3H]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 ([3H]hemicholinium binding) or the muscarinic ([3H]QNB) receptor binding sites in rat cortex. The mechanism of action behind GPEs enhancement of cholinergic transmission is therefore still unknown.
Nilsson-Håkansson
L
L
Department of Pharmacology, University of Uppsala, Sweden.
Civalero
I
I
Zhang
X
X
Carlsson-Skwirut
C
C
Sara
V R
VR
Nordberg
A
A
D000109:Acetylcholine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D006426:Hemicholinium 3 / Q000378:metabolism; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D007457:Iodine Radioisotopes; D009842:Oligopeptides; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D006426:Hemicholinium 3; D007334:Insulin-Like Growth Factor I; D002794:Choline; D000109:Acetylcholine; D011188:Potassium; C062053:glycyl-prolyl-glutamic acid