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 o f NaKATPase in proximal tubular basolateral membranes and reduces phos phate (P-i) and citrate excretion, but has only a small effect on Na e xcretion. The reduction in citrate excretion is consistent with the ob served increase in brush border Na+/H+ exchange. Thus, in Na replete r ats, endogenous D inhibits Na entry into proximal tubular cells, throu gh cotransport with P-i and exchange with H+, and inhibits exit throug h the Na pump. Tonic D inhibition of NaKATPase and Na+/H+ antiporter a ctivity is not found in the SH rats' kidneys, which have defective lin kage of proximal tubular D receptors to adenylate cyclase. The inhibit ory action of endogenous D on P-i reabsorption is retained in SHR kidn eys. This suggests that different signaling systems are responsible fo r the effects of D on NaPi transport and Na+/H+ exchange. In OK cells D inhibits NaPi cotransport (Ki 0.2 mu M). The D effect is not blocked by cAMP, adenylate cyclase, PKA or PKC inhibitors. Thus it appears th at D regulates NaPi transport by a non-cAMP, non-PKC mechanism and is a homeostatic regulator of phosphate reabsorption by SHR.