Broetto-Biazon Ana Carla, Bracht Fabrício, Bracht Livia, Kelmer-Bracht Ana Maria, Bracht Adelar
Laboratory of Liver Metabolism, University of Maringá, 87020900 Maringá, Brazil.
Acta Pharmacol Sin. 2009 Jan;30(1):90-7. doi: 10.1038/aps.2008.7. Epub 2008 Dec 15.
Transformation and possible metabolic effects of extracellular NAD+ were investigated in the livers of mice (Mus musculus; Swiss strain) and rats (Rattus novergicus; Holtzman and Wistar strains).
The livers were perfused in an open system using oxygen-saturated Krebs/Henseleit-bicarbonate buffer (pH 7.4) as the perfusion fluid. The transformation of NAD+ was monitored using high-performance liquid chromatography.
In the mouse liver, the single-pass metabolism of 100 micromol/L NAD+ was almost complete; ADP-ribose and nicotinamide were the main products in the outflowing perfusate. In the livers of both Holtzman and Wistar rats, the main transformation products were ADP-ribose, uric acid and nicotinamide; significant amounts of inosine and AMP were also identified. On a weight basis, the transformation of NAD+ was more efficient in the mouse liver. In the rat liver, 100 micromol/L NAD+ transiently inhibited gluconeogenesis and oxygen uptake. Inhibition was followed by a transient stimulation. Inhibition was more pronounced in the Wistar strain and stimulation was more pronounced in the Holtzman strain. In the mouse liver, no clear effects on gluconeogenesis and oxygen uptake were found even at 500 micromol/L NAD+.
It can be concluded that the functions of extracellular NAD+ are species-dependent and that observations in one species are strictly valid for that species. Interspecies extrapolations should thus be made very carefully. Actually, even variants of the same species can demonstrate considerably different responses.
研究细胞外烟酰胺腺嘌呤二核苷酸（NAD+）在小鼠（小家鼠；瑞士品系）和大鼠（褐家鼠；霍尔茨曼和威斯塔品系）肝脏中的转化及可能的代谢作用。
在开放系统中，使用氧饱和的克雷布斯/亨斯莱特-碳酸氢盐缓冲液（pH 7.4）作为灌注液对肝脏进行灌注。使用高效液相色谱法监测NAD+的转化。
在小鼠肝脏中，100微摩尔/升NAD+的单次通过代谢几乎完全；ADP-核糖和烟酰胺是流出灌注液中的主要产物。在霍尔茨曼大鼠和威斯塔大鼠的肝脏中，主要转化产物为ADP-核糖、尿酸和烟酰胺；还鉴定出大量的肌苷和AMP。以重量计，NAD+在小鼠肝脏中的转化效率更高。在大鼠肝脏中，100微摩尔/升NAD+短暂抑制糖异生和氧摄取。抑制之后是短暂的刺激。在威斯塔品系中抑制更明显，在霍尔茨曼品系中刺激更明显。在小鼠肝脏中，即使在500微摩尔/升NAD+时，也未发现对糖异生和氧摄取有明显影响。
可以得出结论，细胞外NAD+的功能具有物种依赖性，在一个物种中的观察结果仅对该物种严格有效。因此，种间推断应非常谨慎。实际上，即使是同一物种的变体也可能表现出相当不同的反应。
