Lithium stimulation of membrane-bound phospholipase C from PC12 cells exposed to nerve growth factor

LiCl stimulated the formation of inositol monophosphate in PC12 cells that had been exposed to nerve growth factor (NGF) for 4-5 days. Half-maximal accumulation was observed at ~8 mM LiCl. Stimulation of formation of inositol bisphosphate plus inositol trisphosphate was half-maximal at ~1 mM LiCl. With membranes isolated from PC12 cells differentiated with NGF, the hydrolysis of added phosphatidylinositol 4,5-bisphosphate (PIP₂) was stimulated by LiCl in a biphasic manner, with the first stimulation half-maximal at ~0.7 mM and the second half-maximal at ~15 mM LiCl. The apparent K(m) for PIP₂ was lowered in the presence of 1.1 mM LiCl from ~200 to ~70 μM. Membranes from cells grown in the absence of NGF did not respond to LiCl. Although observations with intact cells are difficult to interpret without ambiguity, the results obtained with isolated membranes support our interpretation of the stimulatory action of lithium in the intact PC12 cells.