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Insulin-like growth factors-I and -II differentially regulate endogenous acetylcholine release from the rat hippocampal formation

Item Type:Article
Title:Insulin-like growth factors-I and -II differentially regulate endogenous acetylcholine release from the rat hippocampal formation
Creators Name:Kar, S. and Seto, D. and Dore, S. and Hanisch, U. and Quirion, R.
Abstract:Insulin-like growth factors-I and -II (IGF-I and -II) are structurally related mitogenic polypeptides with potent growth promoting effects. These peptides and their corresponding IGF-I and -II receptors are selectively localized in the brain. To date, most of the effects of IGFs are believed to be mediated by IGF-I receptors whereas the significance of IGF-II receptor in mediating biological responses remains unclear. In the present study, we characterized the distribution of IGF-I and IGF-II receptor sites and investigated the effects of both factors on endogenous acetylcholine (ACh) release in adult rat hippocampus. [125I]IGF-I receptor binding sites are recognized by IGF-I> IGF-II> insulin, whereas [125I]IGF-II binding was competed potently by IGF-II> IGF-I but not by insulin. At the cellular level, IGF-I receptor sites were primarily noted in the molecular layer of the dentate gyrus and the CA2-CA3 subfields of the Ammon's horn whereas IGF-II sites were localized predominantly in the pyramidal cell layer of the CA1-CA3 subfields and in the granular cell layer of the dentate gyrus. IGF-I (10(-14)-10(-8) M) and des(1-3) IGF-I (10(-10)-10(-8) M) were found to inhibit whereas IGF-II (10(-14)-10(-8) M) potentiated K+-evoked ACh release from hippocampal slices. Tetrodotoxin altered the effects of IGF-I but not those of IGF-II suggesting that IGF-I acts indirectly via the release of other modulators whereas IGF-II acts directly on or in close proximity to the cholinergic terminals. The inhibitory effects of IGF-I were also observed in the frontal cortex but not in the striatum. In contrast, the stimulatory effects of IGF-II were evident both in the frontal cortex and striatum. Taken together, these results reveal the differential localization of IGF-I and IGF-II receptor sites in the hippocampal formation and the opposite role for these growth factors in the acute regulation of ACh release likely via two distinct mechanisms. Additionally, these data provide the first evidence for a direct role for IGF-II and its receptors in the regulation of transmitter release in the central nervous system.
Keywords:Acetylcholine, Competitive Binding, Hippocampus, IGF Type 1 Receptor, IGF Type 2 Receptor, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Kinetics, Peptide Fragments, Tetrodotoxin, Tissue Distribution, Animals, Rats
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences (U.S.A.)
Page Range:14054-14059
Date:9 December 1997
Official Publication:http://www.pnas.org/content/94/25/14054.abstract
PubMed:View item in PubMed

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