Formation of [3H]inositol metabolites in rat hippocampal formation slices prelabelled with [3H]inositol and stimulated with carbachol.
Rat hippocampal formation slices were prelabelled with [3H]inositol and stimulated with carbachol for times between 7 s and 3 min. The [3H]inositol metabolites in an acid extract of the slices were resolved with anion-exchange HPLC. Carbachol dramatically increased the concentration of [3H]inositol monophosphate, [3H]inositol bisphosphate (two isomers), [3H]inositol 1,3,4-trisphosphate, [3H]inositol 1,4,5-trisphosphate, and [3H]inositol 1,3,4,5-tetrakisphosphate. The levels of [3H]inositol 1,4,5-trisphosphate rose most rapidly; they were maximally elevated after only 7 s and declined toward control levels in 1 min followed by a more sustained elevation in levels for up to 3 min. When [3H]inositol 1,4,5-trisphosphate was incubated with hippocampal formation homogenates in an ATP-containing buffer it was very rapidly metabolised. After 5 min [3H]inositol 1,4-bisphosphate, [3H]inositol 1,3,4-trisphosphate, and [3H]inositol 1,3,4,5-tetrakisphosphate could be detected in the homogenates. Under similar experimental conditions [3H]inositol 1,3,4,5-tetrakisphosphate is metabolised to [3H]inositol 1,3,4-trisphosphate and an inositol bisphosphate isomer that is not [3H]inositol 1,4-bisphosphate. We conclude that like other tissues the primary event in the hippocampus following carbachol stimulation is the activation of phosphatidylinositol 4,5-bisphosphate selective phospholipase C.
Department of Physiology, Medical School, University of Birmingham, England.
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Stephens
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Logan
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D051381:Rats; D014316:Tritium
D007295:Inositol Phosphates; D014316:Tritium; C081655:inositol-1,3,4,5-tetrakisphosphate; C044259:inositol 1,4-bis(phosphate); D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol