Pegg D G, Hook J B
J Pharmacol Exp Ther. 1977 Jan;200(1):65-74.
Organic anion transport capacity measured as accumulation of p-aminohippurate by renal cortical slices was less in kidneys from newborn rats and rabbits than adults and increased with age. Glutathione (GSH) S-aryltransferase activity in 100,000 X g supernatant of renal homogenates, an estimate of GSH-S-transferase concentration in the tissue, was also less in newborn of both species. Enzyme activity increased to adult values by 1 week of age in rats, prior to maturation of transport capacity. Enzyme activity in rabbit kidney was not different at 1 day and 2 weeks but was increased by 4 weeks coincident with transport maturation. In rats, 25 mg/kg of 3-methylcholanthrene administered once a day for 3 days significantly increased enzyme activity but had no effect on transport capacity. Chronic ammonium chloride acidosis increased enzyme activity 8-fold but decreased transport capacity. Forty-eight hours after unilateral nephrectomy in rats transport capacity was significantly increased with little effect on enzyme activity. L-Methionine-SR-sulfoximine (1.85 mmol/kg) significantly reduced glutathione concentration in renal cortex but had no effect on transport capacity. Organic anion transport was greater in male than in in female mice yet there was no difference in enzyme activity between sexes. 3-Methylcholanthrene (10,20, 30 and 40 mg/kg) administered to 2-week-old rabbits twice daily for 3 days increased transport in a dose-dependent manner. GSH S-transferase activity was also increased. Penicillin (90,000 I.U. twice daily for 2 days) similarly increased transport but had no stimulating effect on enzyme activity. The apparent lack of correlation between transport capacity and GSH S-transferase in several instances suggests that GSH S-transferase concentration is probably not the rate-limiting step in renal organic anion transport.
以肾皮质切片对对氨基马尿酸的蓄积来衡量的有机阴离子转运能力，新生大鼠和家兔肾脏中的该能力低于成年动物，且随年龄增长而增加。肾匀浆100,000×g上清液中的谷胱甘肽（GSH）S -芳基转移酶活性，即组织中GSH - S -转移酶浓度的估计值，在这两个物种的新生动物中也较低。大鼠在1周龄时，该酶活性增加至成年水平，此时转运能力尚未成熟。家兔肾脏在1日龄和2周龄时酶活性无差异，但在4周龄时增加，与转运成熟同时发生。在大鼠中，每天一次给予25 mg/kg的3 -甲基胆蒽，连续3天，可显著增加酶活性，但对转运能力无影响。慢性氯化铵酸中毒使酶活性增加8倍，但降低了转运能力。大鼠单侧肾切除48小时后，转运能力显著增加，而对酶活性影响较小。L -蛋氨酸 - SR -亚砜亚胺（1.85 mmol/kg）显著降低肾皮质中的谷胱甘肽浓度，但对转运能力无影响。雄性小鼠的有机阴离子转运能力大于雌性，但两性之间酶活性无差异。对2周龄家兔每日两次给予3 -甲基胆蒽（10、20、30和40 mg/kg），连续3天，转运能力呈剂量依赖性增加。GSH S -转移酶活性也增加。青霉素（每日两次，每次90,000国际单位，连续2天）同样增加了转运，但对酶活性无刺激作用。在几种情况下，转运能力与GSH S -转移酶之间明显缺乏相关性，这表明GSH S -转移酶浓度可能不是肾脏有机阴离子转运的限速步骤。
