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) transport er and the sodium-dependent dicarboxylate transporter of rabbit renal proxi mal tubules are regulated differentially. A variety of protein kinases has been shown to be involved in the regulation of organic anion transport whil e 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 segmen ts of proximal tubules microdissected from rabbit kidneys without the use o f enzymatic agents. H-3-PAH was used as marker substance of the PAH transpo rter, C-14-glutarate as a marker of the sodium/dicarboxylate cotransporter. 30 s tubular uptake measurements were performed. Vanadate (10(-3) M), a se lective inhibitor of tyrosine phosphatase, did not reduce PAH uptake signif icantly, while inhibitors of the serine/threonine phosphatases 1 and 2A, ok adaic 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 th e regulation of renal basolateral PAH transport. There is no effect of thes e phosphatases on basolateral 30s glutarate transport. Thus, additional evi dence for differential regulation of short-time activity of the transporter s for PAH and dicarboxylates is provided. (C) 2000 Editions scientifiques e t medicales Elsevier SAS.