EFFECT OF GAMMA-HEXACHLOROCYCLOHEXANE IN PHOSPHOINOSITIDE SYNTHESIS IN RAT ENTEROCYTES IS CALCIUM-MEDIATED

The influence of the halogenated insecticide lindane, the gamma isomer of hexachlorocyclohexane (gamma-HCH), upon the incorporation of myo-[ 2-H-3]inositol into different phosphoinositide species was analyzed in rat enterocytes. The insecticide decreased the incorporation of myo-[ 2-H-3]inositol into phosphoinositides in a dose- and time-dependent ma nner. The lindane action exhibited a certain degree of specificity as can be deduced from the results obtained when experiments were carried out with different organochlorine compounds: three other hexachlorocy clohexane isomers (alpha-, beta-, and delta-HCH) and two related organ ochlorine insecticides (dieldrin and endrin). Lindane reduced the inco rporation of myo-[2-H-3]-inositol in the three studied phosphoinositid e species (phosphatidylinositol, PI; phosphatidylinositol 4-phosphate, PIP; and phosphatidylinositol 4,5-bisphosphate). However, the lindane effect over PI and PIP synthesis disappeared in the presence of the c alcium chelator EGTA, while phosphatidylinositol synthesis was conside rably increased in both control and lindane-pretreated cells in this e xperimental condition. These results support a mediating role for calc ium in lindane mechanism of action. (C) 1996 Academic Press.