Antagonistic actions of renal dopamine and 5-hydroxytryptamine: Increase in Na+, K+-ATPase activity in renal proximal tubules via activation of 5-HT1A receptors

Abstract

1. 5-Hydroxytryptamine (5-HT) is antinatriuretic. Since this effect of 5-HT is not accomplished by changes in glomerular haemodynamics, we have examined in this study whether 5-HT may influence sodium excretion by affecting the Na+, K+ -ATPase activity in renal cortical tubules. 2. Na+, K+ -ATPase activity was determined as the rate of [32P]-ATP hydrolysis in renal cortical tubules in suspension. Basal Na+ ,K+ -ATPase activity in renal tubules was 4.8±0.4 μmol Pi mg-1 protein h-1 (n = 8). The 5-HT1A receptor agonist, (±)-8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) (10 to 3000 nM) induced a concentration-dependent increase (P < 0.05) in Na+,K+ -ATPase activity with an EC50 value of 355 nM (95% confidence limits: 178, 708). Maximal stimulation elicited by 3000 nM of 8- OH-DPAT was antagonized by the selective 5-HT1A receptor antagonist, (+)-WAY 100135 (10 to 1000 nM) with an IC50 value of 20 nM (14, 29); 0.3 μM (+)-WAY 100135 completely abolished (P < 0.01) the stimulatory effect of 8-OH-DPAT. The stimulatory effect of 8-OH-DPAT was found to be time- dependent (15 ± 2% and 66 ± 7% increase at 2.5 and 5.0 min, respectively). The 5-HT2 receptor agonist α-methyl-5-HT (100 to 3000 nM) did not induce any significant changes in Na+,K+-ATPase activity (5.0 ± 1.5 μmol Pi mg-1 protein h-1; n = 4). 3. The stimulatory effect 8-OH-DPAT was absent when homogenates were used. Stimulation occurred at a Vmax concentration (70 mM) of sodium supporting the notion that stimulation occurs independently of increasing sodium permeability. 4. The inhibitory effect of dopamine (P < 0.05) on Na+,K+ -ATPase activity was blunted by co- incubation with 8-OH-DPAT (0.5 μM). 5. It is concluded that activation of 5-HT1A receptors increases Na+,K+ -ATPase activity in renal cortical tubules; this effect may represent an important cellular mechanism, at the tubule level, responsible for the antinatriuretic effect of 5-HT.