Modulation of Phosphoinositide Hydrolysis by NaF and Aluminum in Rat Cortical Slices

Abstract

NaF stimulated phosphoinositide hydrolysis in rat cortical slices. The production of [³H]inositol monophosphate was rapid for the first 15 min of incubation with NaF, followed by a plateau. The major product detected was [³H]inositol monophosphate, although significant amounts of [³H]inositol bisphosphate and [³H]inositol trisphosphate were also produced. The stimulation of [³H]inositol monophosphate production by NaF was concentration dependent between 2 and 20 μM NaF. Addition of 10 or 100 μM A1C1₃ or aluminum maltol did not alter the effect of NaF, whereas at 500 μM, these aluminum preparations resulted in significant inhibition. Increasing the concentration of K⁺ from 5 to 20 μM potentiated [³H]inositol monophosphate production induced by carbachol but not by NaF. Incubation with 1 μM phorbol 12–myristate 13–acetate, a phorbol ester, inhibited carbachol-induced, but not NaF-induced, [³H]inositol monophosphate production. These results further support the hypothesis that a guanine nucleotide binding protein that can be activated by NaF is involved in phosphoinositide hydrolysis in brain. The use of NaF provides a means to bypass receptors to study intracellular regulatory sites of phosphoinositide metabolism without disrupting cells.