Elevation of cerebrospinal fluid choline levels by nicotinamide involves the enzymatic formation of N1-methylnicotinamide in brain tissue.
Nicotinamide administration can elevate plasma and brain choline levels and produce a marginal increase in striatal acetylcholine levels in the rat. We now report that subcutaneous nicotinamide produces a substantial and long-lasting rise in cisternal cerebrospinal fluid (CSF) levels of choline in free-moving rats, possibly through the enzymatic formation of N1-methylnicotinamide (NMN) in brain. CSF choline levels peaked 2 hours after nicotinamide administration and were accompanied by increases in striatal, cortical, hippocampal and plasma choline levels. The enzymatic formation of [3H]NMN in rat brain was evaluated by incubating aliquots of rat brain cytosol with unlabelled nicotinamide and the methyl donor [3H]S-adenosylmethionine. High performance liquid chromatography and radiochemical detection demonstrated that [3H]NMN was specifically formed by a brain cytosolic enzyme. The production of [3H]NMN was dependent on exogenous nicotinamide and could be prevented by denaturing the cytosol. The metabolism of nicotinamide to NMN in rat brain may explain the rise in CSF choline levels since NMN, a quaternary amine, can inhibit choline transport at the choroid villus and reduce choline clearance.
Vargas
H M
HM
Department of Pharmacology, UCLA School of Medicine 90024-1735, USA.
Jenden
D J
DJ
D000109:Acetylcholine / Q000134:cerebrospinal fluid; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000097:blood / Q000134:cerebrospinal fluid*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D014316:Tritium
D014316:Tritium; D009536:Niacinamide; D012436:S-Adenosylmethionine; D002794:Choline; D000109:Acetylcholine; C024058:N(1)-methylnicotinamide