烟酰胺超载增加血中5-羟色胺和组胺水平
田彦捷, 李达, 马强, 谷新医, 郭明, 伦永志, 孙武平, 王昕源, 曹宇, 周士胜
大连大学医学研究中心,大连 116622;大连大学附属中山医院神经内科,大连 116001;大连大学环化学院,大连 116622;中国医科大学生理学教研室,沈阳 110001
摘要
甲基化是单胺类神经递质儿茶酚胺、5-羟色胺和组胺降解的关键步骤。没有活泼甲基供应,即使催化甲基化反应的转甲基酶正常,甲基化介导的单胺类神经递质降解将不能进行。已知尼亚新(烟酸和烟酰胺)降解消耗体内活泼甲基,而目前食物中添加尼亚新已使高尼亚新饮食非常普遍。然而,过多尼亚新对单胺类神经递质代谢的影响尚不完全清楚。本文旨在观察烟酰胺超载对人5-羟色胺和组胺代谢的影响。9名健康男性志愿者禁食过夜后,口服100 mg烟酰胺,于口服药物前后取尿液和血浆样本。用高效液相色谱法检测血浆甲基化烟酰胺、甜菜碱和尿中N1-甲基-2-吡啶酮-5-羟基胺水平,用试剂盒检测血浆胆碱、组胺和5-羟色胺水平。结果显示,烟酰胺负荷后,受试者血浆甲基化烟酰胺水平和尿中甲基化代谢产物N1-甲基-2-吡啶酮-5-羟基胺排出均增加,而血浆甲基供体甜菜碱水平降低,同时伴5-羟色胺和组胺水平显著增加。以上结果提示过量摄入烟酰胺可引起单胺类神经递质代谢紊乱,这将有助于揭示饮食与单胺代谢紊乱相关疾病(如精神分裂症和自闭症)的关系。
关键词: 烟酰胺; 5-羟色胺; 组胺; 单胺神经递质; 精神疾病; 自闭症
分类号:R338; R749
Excess nicotinamide increases plasma serotonin and histamine levels
TIAN Yan-Jie, Li Da, Ma Qiang, GU Xin-Yi, GUO Ming, LUN Yong-Zhi, SUN Wu-Ping, WANG Xin-Yuan, CAO Yu, ZHOU Shi-Sheng
Institute of Basic Medical Sciences, Medical College, Dalian University, Dalian 116622, China; Department of Neurology, Zhongshan Hospital Affiliated to Dalian University, Dalian 116001, China; College of Environmental and Chemical Engineering, Dalian University, Dalian 116622, China; Department of Physiology, Institute of Basic Medical Sciences, China Medical University, Shenyang 110001, China
Abstract
Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).
Key words: nicotinamide; serotonin; histamine; monoamine neurotransmitters; mental disorders; autism
收稿日期:2012-06-06 录用日期:2012-07-13
通讯作者:周士胜 E-mail: zhouss@dlu.edu.cn
引用本文:
田彦捷, 李达, 马强, 谷新医, 郭明, 伦永志, 孙武平, 王昕源, 曹宇, 周士胜. 烟酰胺超载增加血中5-羟色胺和组胺水平[J]. 生理学报 2013; 65 (1): 33-38.
TIAN Yan-Jie, Li Da, Ma Qiang, GU Xin-Yi, GUO Ming, LUN Yong-Zhi, SUN Wu-Ping, WANG Xin-Yuan, CAO Yu, ZHOU Shi-Sheng. Excess nicotinamide increases plasma serotonin and histamine levels. Acta Physiol Sin 2013; 65 (1): 33-38 (in Chinese with English abstract).