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

Détails

ID Serval
serval:BIB_01CF9BB2D9F3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Transport of methotrexate by the in vitro isolated rabbit proximal tubule.
Périodique
Journal of Pharmacology and Experimental Therapeutics
Auteur⸱e⸱s
Besseghir K., Mosig D., Roch-Ramel F.
ISSN
0022-3565
Statut éditorial
Publié
Date de publication
1989
Peer-reviewed
Oui
Volume
250
Numéro
2
Pages
688-695
Langue
anglais
Résumé
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.
Mots-clé
Absorption, Animals, Biological Transport, Female, Folic Acid/pharmacology, Kidney Tubules, Proximal/metabolism, Male, Methotrexate/pharmacokinetics, Perfusion, Probenecid/pharmacology, Rabbits
Pubmed
Web of science
Création de la notice
17/07/2009 16:25
Dernière modification de la notice
20/08/2019 12:24
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