Transport of methotrexate by the in vitro isolated rabbit proximal tubule.

Details

Serval ID
serval:BIB_01CF9BB2D9F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transport of methotrexate by the in vitro isolated rabbit proximal tubule.
Journal
Journal of Pharmacology and Experimental Therapeutics
Author(s)
Besseghir K., Mosig D., Roch-Ramel F.
ISSN
0022-3565
Publication state
Published
Issued date
1989
Peer-reviewed
Oui
Volume
250
Number
2
Pages
688-695
Language
english
Abstract
The tubular transport of [3H]methotrexate was studied in isolated nonperfused and perfused superficial proximal tubular segments of rabbit kidneys. Reabsorption represented only 5% of perfused methotrexate, and appeared to be mostly of passive nature inasmuch as it was not modified by reducing the temperature or by ouabain. Cellular accumulation in nonperfused segments and secretion in perfused tubules were highest in the S2 segment and lower in the S3 and S1 segments. Secretion against a bath-to-lumen concentration gradient was observed only in S2 segments (with a maximum methotrexate secretory rate of 478 +/- 48 fmol/mm.min and an apparent Km of transport of 363 +/- 32 microM), and was inhibited by probenecid and folate. The low capacity for methotrexate secretion may be explained by a low capacity of transport across the basolateral membrane of the proximal cell as methotrexate was accumulated only to a low extent in nonperfused tubules (tissue water to medium concentration ratio of 8.2 +/- 1 in S2 segments). During secretion a small amount of methotrexate was metabolized; the nature of the metabolite(s) remains to be defined.
Keywords
Absorption, Animals, Biological Transport, Female, Folic Acid/pharmacology, Kidney Tubules, Proximal/metabolism, Male, Methotrexate/pharmacokinetics, Perfusion, Probenecid/pharmacology, Rabbits
Pubmed
Web of science
Create date
17/07/2009 16:25
Last modification date
20/08/2019 12:24
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