Involvement of protein phosphatases in differential regulation of renal proximal tubular PAH and sodium-dependent dicarboxylate transport

It has been demonstrated that the basolateral organic anion (PAH) transporter and the sodium-dependent dicarboxylate transporter of rabbit renal proximal tubules are regulated differentially. A variety of protein kinases has been shown to be involved in the regulation of organic anion transport while dicarboxylate uptake, to which the first is coupled functionally, is not influenced by these kinases. This study was undertaken to elucidate whether respective transporter activities are modulated differentially by protein phosphatases as well. The experiments were performed on isolated S-2 segments of proximal tubules microdissected from rabbit kidneys without the use of enzymatic agents. H-3-PAH was used as marker substance of the PAH transporter, C-14-glutarate as a marker of the sodium/dicarboxylate cotransporter. 30 s tubular uptake measurements were performed. Vanadate (10(-3) M), a selective inhibitor of tyrosine phosphatase, did not reduce PAH uptake significantly, while inhibitors of the serine/threonine phosphatases 1 and 2A, okadaic acid and calyculin A (10(-6) M, each) induced a significant decrease of 30 a PAH uptake (by 32.3% +/- 7.9% and 25.6% +/-: 6.4%) but not a change in dicarboxylate transport. These Endings indicate that, in addition to a variety of protein kinases, serine/threonine phosphatases have a role in the regulation of renal basolateral PAH transport. There is no effect of these phosphatases on basolateral 30s glutarate transport. Thus, additional evidence for differential regulation of short-time activity of the transporters for PAH and dicarboxylates is provided. (C) 2000 Editions scientifiques et medicales Elsevier SAS.