Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells.
Oral administration of CDP-choline to rats raises plasma and brain cytidine levels and increases brain levels of phosphatidylcholine (PC). In contrast, in humans oral CDP-choline increases plasma levels of uridine. To determine whether uridine can also enhance PC synthesis, we developed an assay for CDP-choline, an immediate and rate-limiting precursor in PC synthesis, and measured this intermediate in clonal PC12 rat pheochromocytoma cells incubated with various concentrations of uridine or cytidine. Addition of uridine (50-100 microM) to the incubation medium caused significant elevations in UTP, CT, USAP and CDP-choline levels in PC12 cells. Uridine had no effect on the synthesis of diacylglycerol (DAG) or the activity of the phosphotransferase which catalyzes the synthesis of PC from DAG and CDP-choline. Hence uridine treatment was unlikely to inhibit the conversion of endogenous CDP-choline to PC. These results suggest the possibility that uridine may also enhance PC synthesis in intact brain.
Richardson
U Ingrid
UI
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ingrid@mit.edu
Watkins
Carol J
CJ
Pierre
Celine
C
Ulus
Ismael H
IH
Wurtman
Richard J
RJ
D000818:Animals; D003562:Cytidine / Q000494:pharmacology*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism*; D004075:Diglycerides / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000032:analysis; D051381:Rats; D013997:Time Factors; D014529:Uridine / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000378:metabolism
D004075:Diglycerides; D010713:Phosphatidylcholines; D003566:Cytidine Diphosphate Choline; D003562:Cytidine; D020932:Nerve Growth Factor; D014544:Uridine Triphosphate; D014529:Uridine