Effect of dopamine on sodium uptake by renal proximal tubule cells of rabbit.
Although dopamine is known to be natriuretic, it is not clear if this is due to changes in renal hemodynamics or to a direct tubular effect. Studies on the effect of dopamine on proximal sodium reabsorption have yielded conflicting information, both an increase and a decrease in sodium reabsorption has been reported. The present study examines the direct effect of dopamine on sodium uptake in proximal renal cells and the possible mechanisms involved. Dopamine (10(-7)-10(-4) M) stimulated in a dose-dependent manner sodium uptake by proximal renal cells by 35-92%; 1 mM ouabain and 70 microM cycloheximide did not modify the effect of dopamine. Kinetic analysis of sodium uptake by these cells showed a single saturable component, inhibitable by amiloride, with a Km of 80 +/- 6 mM and Vmax of 68 +/- 9 pmol/mg protein/min. Dopamine (10(-4) M) increased the Vmax of sodium uptake by 54 +/- 10.3% and had no effect on the Km. Metoclopramide abolished the stimulatory effect of dopamine on sodium uptake whereas propranolol had no effect. Epinine (a dopamine agonist) also stimulated sodium uptake by these cells. We conclude that dopamine directly stimulates sodium uptake in proximal renal cells; this suggests the natriuretic effect of dopamine in whole animals is due to changes in renal hemodynamics and distal tubular effects; dopamine increases the Vmax of the sodium transporter and not the Km; the sensitivity of sodium uptake to amiloride suggests that dopamine stimulates Na+-H+ exchanger, and the stimulation of sodium uptake by dopamine is independent of Na+-K+-ATPase and new protein synthesis and occurs via the dopamine receptor.
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003846:Deoxyepinephrine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D003513:Cycloheximide; D012964:Sodium; D008787:Metoclopramide; D003846:Deoxyepinephrine; D004298:Dopamine