BIPHASIC EFFECTS OF DOPAMINE ON 86RUBIDIUM UPTAKE IN RAT RENAL PROXIMAL TUBULES

Abstract

The mechanism(s) by which dopamine inhibits Na+ -K+ -ATPase activity in the renal proximal tubule is still controversial. We studied the short-term effects of dopamine on the sodium pump in rat renal proximal tubule suspensions with the 86Rb uptake method. Dopamine and the D1-like agonist, SKF81297, initially stimulated Na+ -K+ -ATPase activity at 5 min and subsequently inhibited it at 10 min and 20 min; the inhibition by 10 μM dopamine at 20 min was 21.3 ± 4.5 %. The inhibitory effect of dopamine on Na+ -K+ -ATPase activity was mimicked by thymeleatoxin (a classical protein kinase C [PKC] agonist) while Sp-8-CPT-cAMPS (a protein kinase A [PKA] agonist) had no effect. However, the combination of the PKC and PKA agonists mimicked the biphasic effects of dopamine and SKF81297. Rp-8-CPT-cAMPS (a PKA inhibitor), U-73122 (a phospholipase C inhibitor), or calphostin C (a PKC inhibitor), blocked the dopamine-mediated biphasic effects on Na+ -K+ -ATPase activity. It is suggested that the biphasic effects of dopamine on Na+ -K+ -ATPase activity (an initial stimulation and a subsequent inhibition) are transduced by activating both PKA and PKC through a D1-like receptor.