Dass P D, Bautista N S, Hardman S H, Lawson L R, Kurtz I
Department of Pathology, Loyola University Medical Center, Maywood, IL 60153.
Life Sci. 1991;48(8):723-31. doi: 10.1016/0024-3205(91)90086-q.
The mechanism by which benzoate enhances total nitrogen excretion was investigated in-situ and in separated rat renal proximal tubules. Orally administered benzoate augmented NH4+, urea and hippurate excretion 2, 1.9 and 76 fold respectively, as compared to baseline for control. Hippurate had similar effects. Benzoate augmented renal blood flow, glutamine extraction and total NH4+ production. Arterio-venous concentration differences of glutamine, glutamate, and NH4+ across the kidney, liver and gut demonstrated an increase in glutamine uptake by the kidney despite reduced release and uptake by the liver and gut, respectively; glutamate release by the kidney and gut was increased; NH4+ handling was unchanged at these three organs. Studies in separated rat renal proximal tubules demonstrated that benzoate stimulated glutamine dependent ammonia-genesis by activation of gamma-glutamyltransferase, via the synthesis of hippurate. The results demonstrate that benzoate can modulate the interorgan partitioning of nitrogen metabolites across several organs, the net effect of which is physiologically expressed as enhanced NH4+ , urea and hippurate excretion.
在原位和分离的大鼠肾近端小管中研究了苯甲酸盐增强总氮排泄的机制。与对照组基线相比,口服苯甲酸盐使NH4+、尿素和马尿酸盐排泄分别增加了2倍、1.9倍和76倍。马尿酸盐有类似的作用。苯甲酸盐增加肾血流量、谷氨酰胺摄取和总NH4+生成。肾脏、肝脏和肠道中谷氨酰胺、谷氨酸和NH4+的动静脉浓度差表明,尽管肝脏和肠道中谷氨酰胺的释放和摄取分别减少,但肾脏对谷氨酰胺的摄取增加;肾脏和肠道中谷氨酸的释放增加;这三个器官对NH4+的处理没有变化。对分离的大鼠肾近端小管的研究表明,苯甲酸盐通过合成马尿酸盐激活γ-谷氨酰转移酶,刺激依赖谷氨酰胺的氨生成。结果表明,苯甲酸盐可以调节氮代谢物在多个器官之间的分配,其净效应在生理上表现为NH4+、尿素和马尿酸盐排泄增加。