Miyamoto Y, Ganapathy V, Leibach F H
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta.
J Pharmacol Exp Ther. 1990 Jan;252(1):98-103.
We investigated the influence of acute renal failure induced by injection of uranyl nitrate on renal handling of peptides in rats. Urinary excretion of brush-border peptidases increased significantly as a result of uranyl nitrate treatment. H+-coupled Gly-Sar uptake was reduced in renal brush-border vesicles from uranyl nitrate-treated rats compared to control rats. The impairment of dipeptide uptake was evident whether the uptake was measured in the presence or absence of a H+ gradient. Kinetic analysis indicated that the impairment was due mainly to a decrease in the maximal velocity of the transporter. beta-Casomorphin, a pentapeptide, was hydrolyzed to di- and tripeptides by dipeptidylpeptidase IV and the hydrolytic products were taken up actively into control brush-border vesicles via the peptide transporter. But in uranyl nitrate-treated rats, the capacity to hydrolyze and transport beta-casomorphin was greatly reduced. These results show that the ability of the kidneys to process peptides is significantly impaired as a result of uranyl nitrate-induced acute renal failure.
我们研究了注射硝酸铀酰诱导的急性肾衰竭对大鼠肾脏处理肽的影响。硝酸铀酰处理导致刷状缘肽酶的尿排泄显著增加。与对照大鼠相比，硝酸铀酰处理大鼠的肾刷状缘小泡中H⁺偶联的甘氨酰-肌氨酸摄取减少。无论在有或无H⁺梯度的情况下测量摄取，二肽摄取的损害都很明显。动力学分析表明，这种损害主要是由于转运体最大速度的降低。β-酪蛋白吗啡，一种五肽，被二肽基肽酶IV水解为二肽和三肽，水解产物通过肽转运体被主动摄取到对照刷状缘小泡中。但在硝酸铀酰处理的大鼠中，水解和转运β-酪蛋白吗啡的能力大大降低。这些结果表明，硝酸铀酰诱导的急性肾衰竭导致肾脏处理肽的能力显著受损。
