Mechanism of dopamine inhibition of renal phosphate transport

Abstract

Dopamine (DA) is natriuretic and phosphaturic. However, whether the effect of DA on Pi reabsorption is a consequence of its effect on sodium transport is not known. Therefore, this study was performed to determine the effect of DA on the maximal transport of phosphate (TmPi), and upon the capacity of renal proximal brush border membrane (BBM) for (Naextra-vesicular, > Naintravesicular)-gradient-dependent transport of Pi, as compared with the transport of other solutes. Graded infusions of Pi (0, 1, 2, and 3 μmol/min) were given to thyroparathyroidectomized male Sprague-Dawley rats in the presence of vehicle (0.9% NaCl; N=5), DA 15 μg/kg/min; N=6), or parathyroid hormone ((PTH); 1 U/kg/min; N=5). The TmPi for rats infused with DA (3.3 ± 0.3 μmol/mL) was significantly less than the Tmpi, for saline control rats (4.4 ± 0.2 μmol/mL). Rats infused with PTH exhibited the lowest TmPi (1.8 ± 0.3 μmol/mL). No differences in sodium excretion were observed among any of the groups. Na-dependent Pi transport was studied in BBM vesicles (BBMV) prepared from rats fed a low-phosphate diet for 2 days that were anesthetized, acutely thyroparathyroidectomized, and systemically infused with DA (350 μg bolus, plus 35 μg/kg/min; N/=8), PTH (33 U/kg bolus, followed by a continuous infusion of 1 U/kg/ min; N=6), or vehicle (1 mL/kg bolus, plus 2 mL/h constant infusion of 0.9% NaCl; N=8) for 90 min. DA significantly inhibited the Na cotransport of Pi by 22.4 ± 4.1% (P < 0.01) as compared with the control group. No effect of DA on the Na cotransport of proline, glucose, or sulfate was observed in the same BBMV. The inhibitory effect of DA on P, uptake was half that produced by a maximal phosphaturic dose of PTH (45.2 ± 3.9%). It was concluded that DA inhibits the Na-Pi cotransporter.