Attenuation of diacylglycerol signal in the primordial human placenta: Role of phosphatidylcholine formation

Abstract

Metabolic conversion of the synthetic DAG, dioctanoylglycerol (DOCG) into the dioctanoyl species of phosphatidic acid (PA docg) and phosphatidylcholine (PC docg) in minced human primordial placenta incubated with [ 32P]phosphate was studied. Time-course experiments performed with 0.25 mM DOCG revealed a much higher capacity of the placenta to synthetize PC docg than PA docg and indicated the rapid metabolism of PC docg. In addition, DOCG stimulated the labeling of PC whereas no such effects on the labeling of lyso-PC and PA were observed. This effect of DOCG is not related to the synthesis of PC de novo, because DOCG did not exhibit any stimulating effect on the synthesis of PC from [ 3H]glycerol or [ 3H]glucose. Experiments with varying concentrations of DOCG (0.025–0.5 mM) showed increasing rate of formation of PC DOCG over a concentration range from 0.05 to 0.5 mM whereas 0.5 mM DOCG was the lowest concentration where significant formation of PA docg was found. Labeling of PC was about 30% over control at 0.125 mM as well as at 0.25 mM DOCG, and decreased below the control level at 0.5 mM DOCG. Labeling of PA and PI was not influenced by these DOCG concentrations. Labeling of PC, either stimulated by DOCG or not, was more sensitive to the inhibitory effect of 1 mM of the DAG analog: dioctanoylethyleneglycol (DOEG) than that of PA. Moreover, 1 mM DOEG inhibited the formation of PC docg without such an effect on the labeling of PA docg. These findings indicate that in the primordial human placenta PC synthesis represents a more efficient attenuation pathway of DAG signal than the formation of PA by DAG kinase.