Springate J, Rennick B, Palumbo P, Bruckenstein D, Acara M
Department of Pharmacology, State University of New York, Buffalo.
J Pharmacol Exp Ther. 1988 Mar;244(3):797-801.
The renal tubular transport and metabolism of nicotinic acid (NA) were investigated using the Sperber technique in unanesthetized hens. Infusion of [14C]NA into the avian renal portal circulation at 10(-10) mol/kg/min revealed that the 14C label was actively transported into urine at a rate 74% that of simultaneously infused tetraethylammonium. Increases in NA infusion rates enhanced 14C label transport so that it eventually equalled the excretion rate of tetraethylammonium. At a NA infusion rate of 10(-8) mol/kg/min, this transport was not affected by probenecid, pyrazinoic acid or p-aminohippurate. Above infusion rates of 10(-7) mol/kg/min, saturation of 14C label transport was reached. Electrophoretic analysis of the 14C label excreted in urine at NA infusion rates less than 10(-7) mol/kg/min revealed a single, unidentified metabolite. At infusion rates greater than 10(-7) mol/kg/min, both the radiolabeled metabolite and [14C]NA were found in the urine. We conclude that NA is transported by a specific mechanism into the avian tubule cell where it is metabolized. As the body's load of this vitamin increases, NA is excreted first in the form of a metabolite and then as both metabolite and unutilized NA.
采用斯珀伯技术,在未麻醉的母鸡身上研究了烟酸(NA)的肾小管转运和代谢。以10(-10)摩尔/千克/分钟的速率将[14C]NA注入鸟类肾门静脉循环,结果显示14C标记物以相当于同时注入的四乙铵74%的速率被主动转运到尿液中。NA输注速率的增加增强了14C标记物的转运,使其最终与四乙铵的排泄速率相等。在NA输注速率为10(-8)摩尔/千克/分钟时,这种转运不受丙磺舒、吡嗪酸或对氨基马尿酸的影响。在输注速率高于10(-7)摩尔/千克/分钟时,14C标记物的转运达到饱和。对NA输注速率低于10(-7)摩尔/千克/分钟时尿液中排泄的14C标记物进行电泳分析,发现了一种单一的、未鉴定的代谢产物。在输注速率高于10(-7)摩尔/千克/分钟时,尿液中同时发现了放射性标记的代谢产物和[14C]NA。我们得出结论,NA通过一种特定机制被转运到鸟类肾小管细胞中并在其中代谢。随着体内这种维生素负荷的增加,NA首先以代谢产物的形式排泄,然后以代谢产物和未利用的NA的形式排泄。