Membrane effects of phorbol esters.

Abstract

Tetradecanoyl-phorbol-acetate (TPA) was observed to produce a 15% decrease in the electrophoretic mobility of hyperdiploid Ehrlich-Lettre ascites tumor cells (ELD). This reduction in mobility of ELD was capable of being reversed by washing the cells in Ca2+-free Krebs-Ringer phosphate. An inactive phorbol stereoisomer (4α-phorbol-didecanoate) did not reduce the mobility of ELD. Effects of TPA on enzyme-treated cells lead us to suggest that TPA interacts with sites separate from those acted upon by neuraminidase but that TPA interacts with sites that are also acted upon by RNase. In contrast to the above effects on a surface membrane property of ELD, TPA failed to stimulate the activity of a surface membrane enzyme, (Na+ + K+)-ATPase of ELD homogenates. The (Na+ + K+)-ATPase activity of rat glioma or 3T3 cells was also unaffected. TPA did, however, at 10-5 m inhibit the (Na+ + K+)-ATPase of beef brain microsomes by 50%. TPA also failed to stimulate 86Rb+ uptake by ELD; instead, slight inhibitory effects were observed at 10-5 m. Nor did it stimulate the uptake of 86Rb+ by mouse skin sections. However, slight stimulation was observed with 3T3 cells.