CYCLOSPORINE INHIBITS PHOSPHATE-TRANSPORT AND STIMULATES ALKALINE-PHOSPHATASE ACTIVITY IN RENAL BBMV

被引:23
作者
DEMEULE, M
BELIVEAU, R
机构
[1] UNIV QUEBEC,DEPT CHIM,MEMBRANOL MOLEC LAB,CP 8888,SUCC A,MONTREAL H3C 3P8,QUEBEC,CANADA
[2] UNIV MONTREAL,RECH TRANSPORT MEMBRANAIRE GRP,MONTREAL H3C 3J7,QUEBEC,CANADA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1991年 / 260卷 / 04期
关键词
BRUSH-BORDER MEMBRANE VESICLES; PROXIMAL TUBULE; AMINO ACID TRANSPORT; GLUCOSE TRANSPORT; PHOSPHATE UPTAKE; RENAL REABSORPTION;
D O I
10.1152/ajprenal.1991.260.4.F518
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The activity of various enzymes and transport systems was studied in renal brush-border membrane vesicles (BBMV) isolated from rats injected daily with cyclosporin. Alkaline phosphatase (AP) was strongly stimulated: 55 and 113% increases were obtained in BBMV isolated from rats injected with 10 mg cyclosporin/kg for 5 and 10 days. The affinity of the enzyme remained unaltered, but maximal activity (V(max)) showed a strong increase of 2.4-fold between control and treated animals. In addition to the phosphatase activity, phosphate binding to AP also showed a dose-dependent stimulation by cyclosporin treatment: 44 and 70% increases in animals treated for 5 days with 5 and 10 mg cyclosporin/kg. However, the activity of aminopeptidase M was not affected by these treatments, and polyacrylamide gel electrophoresis of BBMV revealed no alterations in the profile of membrane proteins, suggesting the specificity of cyclosporin interaction with alkaline phosphatase. Na+-dependent amino acid and D-glucose transport systems remained unaffected by cyclosporin treatment. The Na+-independent transport system for lysine and the Na+-H+ antiporter activity were also unaltered. In contrast, the initial rate of phosphate uptake decreased by 28% after administration of cyclosporin (10 mg/kg) for 5 days: the Michaelis constant (K(m)) and V(max) decreased from 137 to 85-mu-M and from 1.49 to 1.07 pmol.mu-g-1.5 s-1, respectively. "In vitro" studies with membranes isolated from untreated rats were also undertaken by preincubating membranes with cyclosporin. Neither alkaline phosphatase nor the transport systems were affected under these conditions. These results indicate that cyclosporin has a specific effect on two activities associated with phosphate metabolism but does not interfere on a short-term basis with renal reabsorption of other solutes or with urinary acidification by the Na+-H+ antiporter in proximal tubules.
引用
收藏
页码:F518 / F524
页数:7
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