Broetto-Biazon Ana Carla, Bracht Adelar, Ishii-Iwamoto Emy Luiza, de Moraes Silva Valquíria, Kelmer-Bracht Ana Maria
Laboratory of Liver Metabolism, Department of Biochemistry, University of Maringá, 87020-900 Maringá, Brazil.
Eur J Pharmacol. 2004 Jan 26;484(2-3):291-301. doi: 10.1016/j.ejphar.2003.11.024.
The action of NAD+ on hemodynamics and metabolism of the isolated perfused rat liver was investigated. Extracellular NAD+ (20-100 microM) stimulated glycogen breakdown (glucose release) and inhibited oxygen uptake. Lactate production was predominantly increased, and pyruvate production was predominantly inhibited. NAD+ also increased the portal perfusion pressure. All metabolic effects were strictly Ca2+-dependent. The effects were absent when Ca2+ was excluded, and reintroduction of the cation restored the effects. In preloaded livers, NAD+ accelerated 45Ca2+ efflux. The action of NAD+ was sensitive to three inhibitors of eicosanoid synthesis, suggesting that this action is mediated by these compounds, which are known to be produced and released by Kupffer and endothelial cells. It is impossible to infer from the available data if NAD+ exerts all these effects by itself or if they are caused by one or more of its extracellular hydrolysis products. Nicotinamide was ineffective and can be excluded, but especially cyclic ADP-ribose and ADP-ribose are possibilities that should be considered in future work.
研究了NAD⁺对离体灌注大鼠肝脏血流动力学和代谢的作用。细胞外NAD⁺（20 - 100微摩尔）刺激糖原分解（葡萄糖释放）并抑制氧气摄取。乳酸生成主要增加，丙酮酸生成主要受抑制。NAD⁺还增加门静脉灌注压力。所有代谢效应均严格依赖Ca²⁺。当排除Ca²⁺时效应消失，重新引入阳离子可恢复效应。在预加载的肝脏中，NAD⁺加速⁴⁵Ca²⁺外流。NAD⁺的作用对三种类花生酸合成抑制剂敏感，表明该作用由这些化合物介导，已知这些化合物由库普弗细胞和内皮细胞产生和释放。根据现有数据无法推断NAD⁺是自身发挥所有这些作用，还是由其一种或多种细胞外水解产物引起。烟酰胺无效，可以排除，但特别是环ADP - 核糖和ADP - 核糖是未来工作中应考虑的可能性。
