Perturbation of rat renal tubule transport of the organic cation amantadine in recent onset streptozotocin-induced diabetes and in uninephrectomy

The effects of early-stage diabetes mellitus and uninephrectomy on the rena l tubule transport of amantadine were investigated. Kidney tubules were iso lated from streptozotocin-induced diabetic (+/- insulin treatment), unineph rectomized, and control male Sprague-Dawley rats. There were no differences in the K-m of amantadine uptake in renal proximal and distal tubules for t he imposed treatments compared with control values. V-max for amantadine up take in the proximal tubules of diabetic and uninephrectomized rats was hig her than the respective control (P < 0.05). V-max for insulin-treated diabe tic rats was similar to control values but was lower than that for untreate d diabetic rats (P < 0.05). V-max for distal tubule uptake was not altered by any treatment. Structure-activity studies demonstrated that bicarbonate- dependent amantadine uptake was inhibited by glycolate and lactate, but not by propionate or alpha-, beta-, or gamma -hydroxybutyrate. Early stage str eptozotocin-induced diabetes mellitus and uninephrectomy induced changes in the kidney that resulted in a similar selective increase in proximal tubul e amantadine uptake. These data represent the first description that experi mentally induced diabetes mellitus and uninephrectomy modulate the function of the renal tubule organic cation (amantadine) transport system. Both int erventions represent potential models in which phenotypic modulation of the renal elimination of organic cationic drugs may be achieved and studied.