Na+,K+pump and Na+-coupled ion carriers in isolated mammalian kidney epithelial cells: regulation by protein kinase C

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Abstract
This review updates our current knowledge on the regulation of Na+/H+exchanger, Na+,K+,Cl-cotransporter, Na+,Picotransporter, and Na+,K+pump in isolated epithelial cells from mammalian kidney by protein kinase C (PKC). In cells derived from different tubule segments, an activator of PKC, 4beta-phorbol 12-myristate 13-acetate (PMA), inhibits apical Na+/H+exchanger (NHE3), Na+,Picotransport, and basolateral Na+,K+cotransport (NKCC1) and augments Na+,K+pump. In PMA-treated proximal tubules, activation of Na+,K+pump probably plays a major role in increased reabsorption of salt and osmotically obliged water. In Madin-Darby canine kidney (MDCK) cells, which are highly abundant with intercalated cells from the collecting duct, PMA completely blocks Na+,K+,Cl-cotransport and decreases the activity of Na+,Picotransport by 30-40%. In these cells, agonists of P2purinoceptors inhibit Na+,K+,Cl-and Na+,Picotransport by 50-70% via a PKC-independent pathway. In contrast with MDCK cells, in epithelial cells derived from proximal and distal tubules of the rabbit kidney, Na+,K+,Cl-cotransport is inhibited by PMA but is insensitive to P2receptor activation. In proximal tubules, PKC-induced inhibition of NHE3 and Na+,Picotransporter can be triggered by parathyroid hormone. Both PKC and cAMP signaling contribute to dopaminergic inhibition of NHE3 and Na+,K+pump. The receptors triggering PKC-mediated activation of Na+,K+pump remain unknown. Recent data suggest that the PKC signaling system is involved in abnormalities of dopaminergic regulation of renal ion transport in hypertension and in the development of diabetic complications. The physiological and pathophysiological implications of PKC-independent regulation of renal ion transporters by P2purinoceptors has not yet been examined.Key words: Na+/H+exchanger, Na+,K+,Cl-and Na+,Picotransporters, Na+,K+pump, protein kinase C, P2purinoceptor.