Muscarinic Receptor-Mediated Increase in Extracellular Inositol 1,4,5-Trisphosphate Levels in the Rat Hippocampus: An In Vivo Microdialysis Study |
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Authors: | C. Minisclou L. Rouquier J. Benavides B. Scatton Y. Claustre |
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Affiliation: | Synthelabo Recherche (LERS), Biology Department, Bagneux, France |
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Abstract: | Abstract: The extracellular concentration of inositol 1,4,5-trisphosphate (IP3) has been monitored in the ventral hippocampus of the anesthetized rat by using a microdialysis technique coupled to a radioreceptor assay. Three hours after the implantation of the cannula, basal extracellular concentration of IP3 (corrected for a 9% recovery) was 71 n M (0.39 pmol/60-µl fraction) and remained stable for at least 5 h. Local infusion of carbachol for 60 min caused a significant concentration-related increase in extracellular IP3 levels (0, 24, and 57% at 1, 50, and 100 µ M , respectively). Acetylcholine (100 µ M ) and muscarine (100 µ M ) increased IP3 outflow by 40 and 42%, respectively. The effect of carbachol was fully prevented by coinfusion of 10 µ M pirenzepine and reduced by 1 µ M tetrodotoxin indicating that the carbachol response is mediated by neuronal muscarinic receptors. These data demonstrate the feasibility of using microdialysis and a radioreceptor assay to measure IP3 in the extracellular space. This approach could prove useful for the study of the in vivo operation of muscarinic and, by extension, a number of receptors coupled to phosphoinositide turnover. |
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Keywords: | Inositol 1,4,5-trisphosphate Hippocampus Rat Microdialysis Muscarinic receptor |
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