Vargas H M, Jenden D J
Department of Pharmacology, UCLA School of Medicine 90024-1735, USA.
Life Sci. 1996;58(22):1995-2002. doi: 10.1016/0024-3205(96)00190-7.
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.
给予烟酰胺可提高大鼠血浆和脑内胆碱水平，并使纹状体乙酰胆碱水平略有升高。我们现在报告，皮下注射烟酰胺可使自由活动大鼠的脑池脑脊液（CSF）中胆碱水平大幅且持久升高，这可能是通过脑内N1 - 甲基烟酰胺（NMN）的酶促形成实现的。烟酰胺给药后2小时，脑脊液胆碱水平达到峰值，同时纹状体、皮质、海马和血浆胆碱水平也升高。通过将大鼠脑细胞质的等分试样与未标记的烟酰胺和甲基供体[3H]S - 腺苷甲硫氨酸一起孵育，评估大鼠脑内[3H]NMN的酶促形成。高效液相色谱和放射化学检测表明，[3H]NMN是由脑细胞质酶特异性形成的。[3H]NMN的产生依赖于外源性烟酰胺，并且可以通过使细胞质变性来阻止。大鼠脑内烟酰胺代谢为NMN可能解释了脑脊液胆碱水平的升高，因为NMN作为一种季胺，可以抑制脉络丛中的胆碱转运并减少胆碱清除。
