Calcium and the phosphoinositide cycle in WRK-1 cells. Effects of A23187 on metabolism of specific phosphatidylinositol pools.

WRK-1 cells possess a labile, hormone-sensitive pool of phosphatidylinositol which appears to be separate from the stable, hormone-insensitive phosphatidylinositol. It is the sensitive pool which turns over in response to treatment with vasopressin. Addition of the calcium ionophore A23187, on the other hand, selectively stimulates precursor incorporation into the hormone-insensitive pool of phosphatidylinositol, while causing nonspecific breakdown of both pools. The polyphosphoinositides are similarly affected. Ionophore-stimulated breakdown appears to be predominantly phospholipase C-mediated, since there is a concomitant increase in inositol phosphates. These inositol phosphates are localized predominantly in the extracellular medium. Permeabilization of the cells may explain the extracellular location of the breakdown products. When added together with the hormone, A23187, at concentrations greater than 5 X 10(-6) M, inhibits both hormone-induced synthesis and breakdown of phosphatidylinositol. Omission of calcium from the medium abolishes the effects of the ionophore.