ENHANCEMENT OF BRAIN CHOLINE LEVELS BY NICOTINAMIDE - MECHANISM OF ACTION

Following the subcutaneous (s.c.) administration of nicotinamide (10 m mol/kg), the brain and CSF levels of nicotinamide were increased to mi llimolar concentrations, but the concentrations of N-methylnicotinamid e (NMN) in the CSF, and of NMN and NAD(+) in brain tissue were not sig nificantly altered. Concomitantly, nicotinamide caused increases of th e choline levels in the venous brain blood. In hippocampal slices, nic otinamide (1-10 mM) induced choline release in a calcium- and mepacrin e-sensitive manner and, in [H-3]choline-labelled slices, increased the levels of [H-3]]lyso-phosphatidylcholine and [H-3]glycerophosphocholi ne. We conclude that nicotinamide enhances brain choline concentration s by mobilising choline from choline-containing phospholipids, presuma bly via activation of phospholipase A(2) while the formation of NMN do es not contribute to this effect. (C) 1998 Published by Elsevier Scien ce Ireland Ltd. All rights reserved.