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

This review updates our current knowledge on the regulation of Na+/H+ excha nger, Na+,K+,Cl- cotransporter, Na+,P-i cotransporter, and Na+,K+ pump in i solated epithelial cells from mammalian kidney by protein kinase C (PKC). I n cells derived from different tubule segments, an activator of PKC, 4 beta -phorbol 12-myristate 13-acetate (PMA), inhibits apical Na+/H+ exchanger (N HE3), Na+,P-i cotransport, and basolateral Na+,K+ cotransport (NKCCl) and a ugments Na+,K+ pump. In PMA-treated proximal tubules, activation of Na+,Kpump probably plays a major role in increased reabsorption of salt and osmo tically obliged water. in Madin-Darby canine kidney (MDCK) cells, which are highly abundant with intercalated cells from the collecting duct, PMA comp letely blocks Na+,K+,Cl- cotransport and decreases the activity of Na+,P-i cotransport by 30-40%. In these cells, agonists of P-2 purinoceptors inhibi t Na+,K+,Cl- and Na+,P-i cotransport by 50-70% via a PKC-independent pathwa y. In contrast with MDCK cells, in epithelial cells derived from proximal a nd distal tubules of the rabbit kidney, Na+,K+,Cl- cotransport is inhibited by PMA but is insensitive to P-2 receptor activation. In proximal tubules, PKC-induced inhibition of NHE3 and Na+,P-i cotransporter can be triggered by parathyroid hormone. Both PKC and cAMP signaling contribute to dopaminer gic inhibition of NHE3 and Na+,K+ pump. The receptors triggering PKC-mediat ed activation of Na+,K+ pump remain unknown. Recent data suggest that the P KC 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 P-2 purinoceptors has not yet been examined.