HEXADECYLPHOSPHOCHOLINE INHIBITS TRANSLOCATION OF CTP - CHOLINE-PHOSPHATE CYTIDYLYLTRANSFERASE IN MADIN-DARBY CANINE KIDNEY-CELLS

The mechanism of the inhibition of phosphatidylcholine biosynthesis by the phospholipid analogue, hexadecylphosphocholine, was investigated in Madin-Darby canine kidney cells. In the presence of 50-mu-mol/liter hexadecylphosphocholine, there was a translocation of CTP:choline-pho sphate cytidylyltransferase (EC 22.7.7.15) activity from the membranes to the cytosol of the cells. Since we recently demonstrated that hexa decylphosphocholine also inhibits protein kinase C in vitro, [methyl-H -3]choline labeling experiments were repeated with phorbol ester-desen sitized cells. In these cells the same inhibitory effect of hexadecylp hosphocholine was measured. As a consequence of inhibition, the [methy l-H-3]choline incorporation into the phosphocholine pool was increased time-dependently. In addition, there was no evidence for a difference between the choline uptake of control and hexadecylphosphocholine-tre ated cells. Likewise, the amount of diacylglycerol, a known activator of the translocation process, was not reduced. Finally, we showed that the inhibitory effect of hexadecylphosphocholine on CTP:choline-phosp hate cytidylyltransferase translocation cannot be explained by the det ergent properties of this phospholipid analogue. Therefore, we suggest a direct inhibitory effect of hexadecylphosphocholine on the transloc ation of CTP:choline-phosphate cytidylyltransferase.