The relationship between neurite extension and phospholipid metabolism in PC12 cells.

NGF stimulates a variety of changes in PC12 cells. These include neurite extension and an increase in the metabolism of phosphatidylinositol and phosphatidic acid (the so-called 'PI effect'). Cyclic AMP has been postulated to mediate many of the effects of NGF on PC12 cells, and we recently found that a variety of agents which stimulate neurite extension also increase intracellular cyclic AMP. These agents included phospholipase A2 and phospholipase C. In an effort to clarify the relationship of the 'PI effect' to other NGF-induced events we investigated the effects of these agents and of cyclic AMP on phospholipid metabolism. All agents which elevate cyclic AMP stimulate phosphatidylinositol metabolism. In addition, elevated exogenous KCl, which does not stimulate cyclic AMP production, promotes neurite extension and also causes the 'PI effect'. These data suggest that an increase in the turnover of phosphatidylinositol may be a requisite event in neurite outgrowth.