DOPAMINE AND PROTEIN PHOSPHATASE-ACTIVITY IN RENAL PROXIMAL TUBULES

In the brain, dopamine, via protein kinase A (PKA) activation of dopam ine- and cAMP-regulated phosphoprotein (DARPP-32), inhibits protein ph osphatase 1 (PP1) activity and keeps Na+-K+-adenosinetriphosphatase (A TPase) in its phosphorylated inactive state. In the present study, we examined the relationship among dopamine, PP1, and Na+-K+-ATPase activ ities in renal proximal tubules. PP1 activity in proximal tubules was not decreased by dopamine (5 x 10(-9)-10(-4) M), fenoldopam (5 x 10(-6 ) M), or norepinephrine (5 x 10(-7) M). In contrast, in the medullary thick ascending limb of Henle and in the brain striatum, PP1 activity was decreased by fenoldopam (5 x 10(-6) M). We also showed that the ab ility of dopamine (10(-6) M) to inhibit Na+-K+-ATPase activity in prox imal tubules (assessed by ouabain-sensitive Rb-86 uptake) occurred in the absence or presence of a sodium clamp with 5 mu M monensin. Thus t he inhibitory effect of dopamine on Na+-K+-ATPase activity in proximal tubules is not regulated by PP1 activity. Tautomycin and okadaic acid by themselves, at concentrations that inhibited PP1 activity, had no effect-on Na+-K+-ATPase activity in proximal tubules. The ability of a dopamine D-1 agonist, fenoldopam, to inhibit PP1 activity in brain st riatum and in medullary thick ascending limb, but not in proximal tubu les, suggests differential organ and nephron segment regulation of PP activity.