Elsevier

Biochemical Pharmacology

Volume 31, Issue 21, 1 November 1982, Pages 3387-3394
Biochemical Pharmacology

Research paper
Renal transport of 2′-deoxytubercidin in mice

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Abstract

Previous results [J. F. Kuttesch, Jr. and J. A. Nelson, Cancer Chemother. Pharmac.8, 221 (1982)] from this laboratory indicate that mechanisms exist for renal secretion of 2′-deoxyadenosine and possibly for reabsorption of adenosine in humans and in mice. Since significant metabolism of these purine nucleosides occurs even in the presence of adenosine deaminase inhibitors, the renal handling of a compound which is not significantly metabolized by the deaminase or by kinases was studied. Unlike 2′-deoxyadenosine itself, the 2′-deoxyadenosine analog, [4-amino-7-(2′-deoxy-β-D-erythro-pentofuranosyl)-pyrrolo-(2,3d)pyrimidine; 2′-deoxytubercidin], is not significantly metabolized by mammalian tissues. In mice, the renal plasma clearance of 2′-deoxytubercidin exceeded that of inulin by about 3-fold. Also, mouse kidney slices concentratively accumulated 2′-deoxytubercidin by a saturable and metabolically dependent process. The uptake by mouse kidney slices was inhibited by classical substrates for the organic cation secretory system (tetraethylammonium, choline and N1-methylnicotinamide) but was not markedly inhibited by classical substrates for the organic anion secretory system (p-aminohippurate, phenol red and probenecid). Since 2′-deoxytubercidin inhibited the active, concentrative uptake of[14C]tetraethylammonium but failed to inhibit the uptake of p-[14C]aminohippurate by mouse kidney slices, it is concluded that 2′-deoxytubercidin may be secreted by the organic cation system. Additional studies are required, however, to unequivocally establish the relationships between 2′-deoxytubercidin 2′-deoxyadenosine and tetraethylammonium renal secretory mechanisms.

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Cited by (0)

Supported by grants from the U.S. National Institutes of Health (HD-13951 and CA-28034), the National Cancer Institute of Canada, and a John W. McLaughlin Predoctoral Fellowship.

Doctoral candidate, Program in Pharmacology and Toxicology, The University of Texas Medical Branch, Graduate School of Biomedical Sciences at Galveston, Texas.

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