Renal secretion of purine nucleosides and their analogs in mice

Abstract

Previous results have indicated that 2'-deoxyadenosine (dAdo) and 2'-deoxytubercidin (dTub) are secreted by the mouse kidney. Secretion of dTub appeared to occur via the organic cation carrier [J. F. Kuttesch, Jr. et al., Biochem. Pharmac. 31, 3387 (1982)]. In the current study, the structural specificity of the secretory system for d Tub was probed by evaluating the renal clearance of several sugar-modified dTub analogs. The following sugar-modified derivatives also underwent apparent secretion: 3'-deoxy, arabinosyl, and xylosyl. These results suggest a lack of structural specificity of the secretory system for dTub. Tubercidin was apparently reabsorbed, analogous to the observation in mice that adenosine clearance is less than that of inulin. In related experiments, a transport maximum for dAdo could not be demonstrated due to the marked pharmacologic activity of dAdo. Cimetidine was found to selectively inhibit the organic cation secretory system since it blocked the renal secretion of tetraethylammonium but not that of p-amminohippurate in mice. Correspondingly, cimetidine prevented the renal secretion dTub; however, cimetidine did not inhibit the renal secretion of dAdo nor the renal reabsorption of Ado. These results suggest that renal secretion of dTub occurs via the organic cation carrier. The mechanisms for the renal secretion of dAdo and for the renal reabsorption of Ado may be unique and independent of the organic cation system.