| Abstract: | 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. |
