Enhancement of brain choline levels by nicotinamide: mechanism of action

Following the subcutaneous (s.c.) administration of nicotinamide (10 mmol/kg), the brain and CSF levels of nicotinamide were increased to millimolar concentrations, but the concentrations of N-methylnicotinamide (NMN) in the CSF, and of NMN and NAD(+) in brain tissue were not significantly altered. Concomitantly, nicotinamide caused increases of the choline levels in the venous brain blood. In hippocampal slices, nicotinamide (1-10 mM) induced choline release in a calcium- and mepacrine-sensitive manner and, in [H-3]choline-labelled slices, increased the levels of [H-3]]lyso-phosphatidylcholine and [H-3]glycerophosphocholine. We conclude that nicotinamide enhances brain choline concentrations by mobilising choline from choline-containing phospholipids, presumably via activation of phospholipase A(2) while the formation of NMN does not contribute to this effect. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.