EFFECT OF CYTIDINE ON MEMBRANE PHOSPHOLIPID-SYNTHESIS IN RAT STRIATALSLICES

Using rat striatal slices, we examined the effect of cytidine on the c onversion of [H-3]choline to [H-3]-phosphatidylcholine ([H-3]PC), and on net syntheses of PC, phosphatidylethanolamine (PE), and phosphatidy lserine, when media did or did not also contain choline, ethanolamine, or serine. Incubation of striatal slices with cytidine (50-500 mu M) caused dose-dependent increases in intracellular cytidine and cytidine triphosphate (CTP) levels and in the rate of incorporation of [3H]cho line into membrane [H-3] PC. In pulse-chase experiments, cytidine (200 mu M) also increased significantly the conversion of [H-3]choline to [H-3]PC during the chase period. When slices were incubated with this concentration of cytidine for 1 h, small (7%) but significant elevatio ns were observed in the absolute contents (nmol/mg of protein) of memb rane PC and PE (p < 0.05), but not phosphatidylserine, the synthesis o f which is independent of cytidine-containing CTP. Concurrent exposure to cytidine (200 mu M) and choline (10 mu M) caused an additional sig nificant increase (p < 0.05) in tissue PC levels beyond that produced by cytidine alone. Exposure to choline alone at a higher concentration (40 mu M) increased the levels of all three membrane phospholipids (p < 0.01); the addition of cytidine, however, did not cause further inc reases. Concurrent exposure to cytidine (200 mu M) and ethanolamine (2 0 mu M) also caused significantly greater elevations (p < 0.05) in tis sue PE levels than those caused by cytidine alone. In contrast, the ad dition of serine (500 mu M) did not enhance cytidine's effects on any membrane phospholipid. Exposure to serine alone, however, like exposur e to sufficient choline, increased levels of all three membrane phosph olipids significantly (p < 0.01). These data show that exogenous cytid ine, probably acting via CTP and the Kennedy cycle, can increase the s ynthesis and levels of membrane PC and PE in brain cells.