Regulation of sodium transport by endogenous dopamine production in proximal tubular and OK cells.

Inhibition of AADC for several hours increases the activity and mass of NaKATPase in proximal tubular basolateral membranes and reduces phosphate (P1) and citrate excretion, but has only a small effect on Na excretion. The reduction in citrate excretion is consistent with the observed increase in brush border Na+/H+ exchange. Thus, in Na replete rats, endogenous D inhibits Na entry into proximal tubular cells, through cotransport with Pi and exchange with H+, and inhibits exit through the Na pump. Tonic D inhibition of NaKATPase and Na+/H+ antiporter activity is not found in the SH rats' kidneys, which have defective linkage of proximal tubular D receptors to adenylate cyclase. The inhibitory action of endogenous D on Pi reabsorption is retained in SHR kidneys. This suggests that different signaling systems are responsible for the effects of D on NaPi transport and Na+/H+ exchange. In OK cells D inhibits NaPi cotransport (Ki 0.2 microM). The D effect is not blocked by cAMP, adenylate cyclase, PKA or PKC inhibitors. Thus it appears that D regulates NaPi transport by a non-cAMP, non-PKC mechanism and is a homeostatic regulator of phosphate reabsorption by SHR.