Abstract
UDP-glucuronosyltransferase is expressed in the proximal convoluted tubular cells of rat kidney. Kidney perfusion with a Krebs-Henseleit buffer containing 1-naphthol was performed to estimate the dynamics and disposition of the glucuronide conjugate formed in the epithelial cells of the renal tubules. When 1-naphthol was injected into the renal artery, and the perfusate from the renal vein was returned to a reservoir and recirculated through the kidney preparation (recirculating perfusion), most of the 1-napthol was immediately excreted into the vein as a glucuronide conjugate and its concentration increased rapidly. In contrast, the 1-napthol glucuronide appeared more slowly in the urine. 1-Naphthol was also injected during the initial 5 min of perfusion under single-pass perfusion conditions (single-pass perfusion) in situ, and the metabolite and parent compound in the venous perfusate and in urine were assayed. Under this condition, most of the 1-naphthol glucuronide was excreted into the renal vein, and not urine. Phenol UDP-glucuronosyltransferase was highly induced in the rat kidney by β-naphthoflavone treatment. Moreover, the amount of 1-naphthol glucuronide excreted in the renal vein was increased 2.7-fold in the perfused kidney of β-naphthoflavone-treated rats, but the amount in the urine was not significantly increased under singlepass perfusion conditions. These results indicate that the kidney can glucuronidate phenolic xenobiotics in epithelial cells of the tubules and excrete the resultant glucuronide into the renal vein.
Footnotes
-
This work was supported in part by grants-in-aid from the Ministry of Education, Science, Sports and Culture of Japan, by the Science Research Promotion Fund of the Promotion and Mutual Aid Corporation for Private Schools of Japan, by a grant-in-aid for High Technological Research Center (Rakuno Gakuen University) from the Ministry of Education, Science, Sports and Culture of Japan, and by Rakuno Gakuen Ikueikai.
-
ABBREVIATIONS: ABC, ATP-binding cassette; MRP, multidrug resistance-associated protein; HPLC, high-performance liquid chromatography; UGT, UDP-glucuronosyltransferase.
- Received November 4, 2003.
- Accepted April 15, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|