A model of inositol compartmentation in astrocytes based upon efflux kinetics and slow inositol depletion after uptake inhibition

Intracellular compartmentation of inositol was demonstrated in primary cult ures of mouse astrocytes, incubated in isotonic medium, by determination of efflux kinetics after "loading" with [H-3]inositol. Three kinetically diff erent compartments were delineated. The largest and most slowly exchanging compartment had a halflife of similar to 9 hr. This slow release leads to r etention of a sizeable amount of pre-accumulated inositol in the tissue 24 hr after the onset of uptake inhibition, as confirmed by the observation th at the inositol uptake inhibitor fucose caused a larger inhibition of unidi rectional inositol uptake than of inositol pool size, measured as accumulat ed [H-3]inositol after 24 hr of combined exposure to the inhibitor and the labeled isotope. Based upon the present observations and literature data, i t is suggested that the large, slowly exchanging compartment is largely mem brane-associated and participating in signaling via the phosphatidylinositi de second messenger system, whereas inositol functioning as an osmolyte is distributed in the cytosol and located in one or both of the compartments s howing a faster release.