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 [3H]choline-labelled slices, increased the levels of [3H]lyso-phosphatidylcholine and [3H]glycerophosphocholine. We conclude that nicotinamide enhances brain choline concentrations by mobilising choline from choline-containing phospholipids, presumably via activation of phospholipase A2, while the formation of NMN does not contribute to this effect.
Erb
C
C
Pharmakologisches Institut der Universitat Mainz, Germany.
Klein
J
J
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008099:Liver / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009243:NAD; D009536:Niacinamide; D002794:Choline; C008472:N-methylnicotinamide