Oral uridine-5'-monophosphate (UMP) increases brain CDP-choline levels in gerbils.
We examined the biochemical pathways whereby oral uridine-5'-monophosphate (UMP) increases membrane phosphatide synthesis in brains of gerbils. We previously showed that supplementing PC12 cells with uridine caused concentration-related increases in CDP-choline levels, and that this effect was mediated by elevations in intracellular uridine triphosphate (UTP) and cytidine triphosphate (CTP). In the present study, adult gerbils received UMP (1 mmol/kg), a constituent of human breast milk and infant formulas, by gavage, and plasma samples and brains were collected for assay between 5 min and 8 h thereafter. Thirty minutes after gavage, plasma uridine levels were increased from 6.6 +/- 0.58 to 32.7 +/- 1.85 microM (P < 0.001), and brain uridine from 22.6 +/- 2.9 to 89.1 +/- 8.82 pmol/mg tissue (P < 0.001). UMP also significantly increased plasma and brain cytidine levels; however, both basally and following UMP, these levels were much lower than those of uridine. Brain UTP, CTP, and CDP-choline were all elevated 15 min after UMP (from 254 +/- 31.9 to 417 +/- 50.2, [P < 0.05]; 56.8 +/- 1.8 to 71.7 +/- 1.8, [P < 0.001]; and 11.3 +/- 0.5 to 16.4 +/- 1, [P < 0.001] pmol/mg tissue, respectively), returning to basal levels after 20 and 30 min. The smallest UMP dose that significantly increased brain CDP-choline was 0.05 mmol/kg. These results show that oral UMP, a uridine source, enhances the synthesis of CDP-choline, the immediate precursor of PC, in gerbil brain.
Cansev
Mehmet
M
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, E25-604, MIT, Cambridge, MA 02139, USA.
Watkins
Carol J
CJ
van der Beek
Eline M
EM
Wurtman
Richard J
RJ
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D008297:Male; D008563:Membrane Lipids / Q000096:biosynthesis; D010713:Phosphatidylcholines / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D014529:Uridine / Q000097:blood; D014542:Uridine Monophosphate / Q000378:metabolism / Q000494:pharmacology*
D008563:Membrane Lipids; D010713:Phosphatidylcholines; D003566:Cytidine Diphosphate Choline; D014542:Uridine Monophosphate; D014529:Uridine