Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Evaluation of nephrotoxic site in rat proximal tubule: Intrarenal distributions of three enzymes and effects of mercuric chloride and gentamicin on their excretion into urine
Chizuko KOSEKIHitoshi ENDOUJun-ichi SUDOHajime SHIMADAFuminori SAKAI
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1980 Volume 76 Issue 1 Pages 59-69

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Abstract
Intrarenal distributions of three enzymes, γ-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (Al-p) and leucine aminopeptidase (LAP) were determined using six segments of nephrons. These enzymes were localized only in the proximal tubule. Intra-proximal distributions of the enzymes, however, were not uniform. The order of each enzyme activity in three segments of the proximal tubule, S1, S2 and S3 was as follows;
γ-GTP and LAP:=S2≈S3>S1
Al-p: S1≈S2≈S3
With subcutaneous administration of HgCl2 (1.0 mg/kg/day), urinary excretions of all three enzymes were increased from the 1st to the 2nd day and then decreased to the control level. However, after intraperitoneal administration of gentamicin sulfate (40 mg/kg/day), only Al-p activity in urine was significantly increased on the 1st day. Because of the lack of increasing blood levels of these enzymes after treatment, increased urinary excretions of the enzymes probably originate from the kidney, particularly the proximal tubule. The prominently increased excretion of γ-GTP and LAP after HgCl2 treatment means that HgCl2 might damage S2 and S3, because the excretory patterns of the three enzymes were similar to their distribution profiles in S2 and S3. On the other hand, the toxic action of GM may be localized in S1 portion, in which Al-p activity proved to be highest among the three enzymes.
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