Stimulation of uric acid release from the perfused rat liver by platelet activating factor or potassium.
Stimulation of uric acid release from the perfused rat liver by platelet activating factor or potassium.
复制标题
通过血小板激活因子或钾刺激灌注的大鼠肝脏释放尿酸。
DOI：
10.1042/bj2470207
复制
发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Olson,MS
中科院分区：
文献类型：
--
作者：
Hill,CE;Olson,MS
血小板活化因子（AGEPC）或增加灌注液钾浓度（[K+]o），但不是苯肾上腺素的刺激肝糖原分解，导致尿酸释放到灌注大鼠肝脏流出液中的瞬时增加。使用反相h.p.l.c.在灌流液样品的色谱图中鉴别出尿酸，其显示出与真实尿酸共洗脱的峰，以及灌注液样品的A293在尿酸酶存在下降低的事实。尿酸的释放是剂量依赖性的AGEPC和[K+]o，并完全阻断灌注的肝脏预先暴露于5 mM别嘌呤醇，黄嘌呤氧化酶（XOD）的特异性抑制剂。别嘌呤醇可抑制AGEPC、[K+]o升高或苯丙氨酸诱导的门静脉压力升高;抑制作用随药物浓度增加而增强。此外，别嘌呤醇抑制第二阶段的O2摄取和葡萄糖释放特征的浓度的AGEPC或增加[K+]o等于或大于其报告的一半最大浓度的葡萄糖释放。用AGEPC处理肝脏或增加[K+]o不影响冷冻钳夹灌注肝脏提取物中黄嘌呤脱氢酶（XDH）与XOD活性的比率。结果表明，尿酸的产生可能是局部肝窦缺血的一个指标，别嘌呤醇通过抑制XOD依赖性超氧化物的产生，部分保护肝细胞免受AGEPC或[K+]o增加的影响。我们建议，糖原分解反应的第二阶段，这些药物的结果缺血和随后的再灌注。在各种病理生理条件下，肝脏对血管活性激动剂的反应可能涉及体内XOD的激活以及因此O2衍生的自由基产生。
The stimulation of hepatic glycogenolysis by platelet activating factor (AGEPC) or increased perfusate potassium concentration ([K+]o), but not phenylephrine, causes a transient increase in uric acid release into the effluent perfusate of perfused rat livers. Uric acid was identified in chromatograms of perfusate samples using reversed-phase h.p.l.c., which show a peak which co-elutes with authentic uric acid, and by the fact that the A293 of perfusate samples decreases in the presence of uricase. Uric acid release is dose-dependent with respect to both AGEPC and [K+]o, and is blocked completely by prior exposure of the perfused liver to 5 mM-allopurinol, a specific inhibitor of xanthine oxidase (XOD). Allopurinol inhibits the increase in portal vein pressure induced by AGEPC, increased [K+]o or phenylephrine; the inhibitory effect increases with increasing concentrations of the agents. Also, allopurinol inhibits the second phase of O2 uptake and glucose release characteristic of concentrations of AGEPC or increased [K+]o equal to or greater than their reported half-maximal concentration for glucose release. The ratio of xanthine dehydrogenase (XDH) to XOD activity in extracts of freeze-clamped perfused livers is not affected by treatment of the livers with AGEPC or increased [K+]o. The results suggest that uric acid production may be an indicator of ischaemia within localized hepatic sinusoids, and that allopurinol partially protects the hepatocyte from the effects of AGEPC or increased [K+]o by inhibiting XOD-dependent superoxide production. We propose that the second phase of the glycogenolytic response to these agents results from ischaemia and subsequent reperfusion. Activation of XODin vivoand hence O2-derived free radical production may be involved in the response of the liver to vasoactive agonists under a variety of pathophysiological conditions.