Insulin-like growth factors-I and -II differentially regulate endogenous acetylcholine release from the rat hippocampal formation
| Autor: | Satyabrata Kar, Sylvain Doré, D. Seto, Rémi Quirion, U.-K. Hanisch |
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| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty Hippocampus Tetrodotoxin In Vitro Techniques Hippocampal formation Biology Inhibitory postsynaptic potential Binding Competitive Receptor IGF Type 2 Receptor IGF Type 1 Rats Sprague-Dawley Insulin-Like Growth Factor II Internal medicine medicine Animals Tissue Distribution Insulin-Like Growth Factor I Receptor Multidisciplinary Dentate gyrus Biological Sciences Acetylcholine Peptide Fragments Rats Kinetics Endocrinology medicine.anatomical_structure Cholinergic Pyramidal cell medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 94:14054-14059 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.94.25.14054 |
| Popis: | 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. [ 125 I]IGF-I receptor binding sites are recognized by IGF-I> IGF-II> insulin, whereas [ 125 I]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. |
| Databáze: | OpenAIRE |
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