Renal transepithelial transport of nucleosides.
Previous work from this and other laboratories has suggested that the mammalian kidney has unique mechanisms for handling purine nucleosides. For example, in humans and in mice, adenosine undergoes net renal reabsorption whereas deoxyadenosine is secreted [Kuttesch and Nelson: Cancer Chemother. Pharmacol. 8, 221 (1982)]. The relationships between these renal transport systems and classical renal organic cation and anion, carbohydrate, and cell membrane nucleoside transport carriers are not established. To investigate possible relationships between such carriers, we have tested effects of selected classical transport inhibitors on the renal clearances of adenosine, deoxyadenosine, 5'-deoxy-5-fluorouridine (5'-dFUR), and 5-fluorouracil in mice. The secretion of deoxyadenosine and 5'-dFUR, but not the reabsorption of adenosine or 5-fluorouracil, was prevented by the classical nucleoside transport inhibitors, dipyridamole and nitrobenzylthioinosine. Cimetidine, an inhibitor of the organic cation secretory system, also inhibited the secretion of 5'-dFUR, although it did not inhibit deoxyadenosine secretion in earlier studies [Nelson et al.: Biochem. Pharmacol. 32, 2323 (1983)]. The specific inhibitor of glucose renal reabsorption, phloridzin, failed to inhibit the reabsorption of adenosine or the secretion of deoxyadenosine. Failure of the nucleoside transport inhibitors and phloridzin to prevent adenosine reabsorption suggests that adenosine reabsorption may occur via a unique process. On the other hand, inhibition of the net secretion of deoxyadenosine and 5'-dFUR by dipyridamole and nitrobenzylthioinosine implies a role for the carrier that is sensitive to these compounds in the renal secretion (active transport) of these nucleosides.
Nelson
J A
JA
Department of Experimental Pediatrics, University of Texas, M. D. Anderson Hospital and Tumor Institute, Houston 77030.
Vidale
E
E
Enigbokan
M
M
D000818:Animals; D001693:Biological Transport, Active; D002927:Cimetidine / Q000494:pharmacology; D004176:Dipyridamole / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005467:Floxuridine / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D009705:Nucleosides / Q000378:metabolism*
D009705:Nucleosides; D005467:Floxuridine; D004176:Dipyridamole; D002927:Cimetidine; D005472:Fluorouracil; C025034:doxifluridine