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Formation of [ 3 H]Inositol Metabolites in Rat Hippocampal Formation Slices Prelabelled with [ 3 H]Inositol and Stimulated with Carbachol
Author(s) -
Stephens L. R.,
Logan S. D.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb02513.x
Subject(s) - inositol , phosphatidylinositol , inositol trisphosphate , carbachol , inositol phosphate , phospholipase c , stimulation , chemistry , medicine , endocrinology , biology , biochemistry , receptor , signal transduction
Rat hippocampal formation slices were prelabelled with [ 3 H]inositol and stimulated with carbachol for times between 7 s and 3 min. The [ 3 H]inositol metabolites in an acid extract of the slices were resolved with anion‐exchange HPLC. Carbachol dramatically increased the concentration of [ 3 H]inositol monophosphate, [ 3 H]inositol bisphosphate (two isomers), [ 3 H]inositol 1,3,4‐trisphosphate, [ 3 H]inositol 1,4,5‐trisphosphate, and [ 3 H]inositol 1,3,4,5‐tetrakisphos‐phate. The levels of [ 3 H]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 [ 3 H]inositol 1,4,5‐trisphosphate was incubated with hippocampal formation homogenates in an ATP‐containing buffer it was very rapidly metabolised. After 5 min [ 3 H]inositol 1,4‐bisphosphate, [ 3 H]inositol 1,3,4‐trisphosphate, and [ 3 H]inositol 1,3,4,5‐tetrakisphosphate could be detected in the homogenates. Under similar experimental conditions [ 3 H]inositol 1,3,4,5‐tetrakisphosphate is metabolised to [ 3 H]inositol 1,3,4‐trisphosphate and an inositol bisphosphate isomer that is not [ 3 H]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.