Inhibition of proximal convoluted tubule transport by dopamine

Abstract

Background: Dopamine can produce a natriuresis and diuresis independent of changes in renal hemodynamics. However, previous studies have failed to demonstrate an inhibition of transport by dopamine in intact proximal convoluted tubules.

Methods: Rabbit proximal convoluted tubules were perfused in vitro with an ultrafiltrate-like solution and bathed in a serum-like albumin solution.

Results: In the present study, the addition of 10-5 M dopamine to the lumen or bath of proximal convoluted tubules perfused in vitro had no effect on transport. In proximal convoluted tubules, addition of 10-6 M bath norepinephrine increased the rate of volume absorption from 0.65 +/- 0.08 to 0.93 +/- 0.08 nl/mm. min (P < 0.01). Addition of 10-5 M luminal dopamine in the presence of bath norepinephrine inhibited the rate of volume absorption to 0.72 +/- 0.10 nl/mm. min (P = 0.01). The inhibition in the rate of volume absorption by luminal dopamine in the presence of bath norepinephrine was completely blocked by the DA1 antagonist, SCH 23390. The DA1 agonist luminal 10-5 M fenoldopam also inhibited volume absorption in the presence of bath norepinephrine, but the DA2 agonist luminal 10-5 M quinpirole was without effect. Bath 10-5 M dopamine had no effect on volume absorption in the presence of bath norepinephrine.

Conclusion: Dopamine has no direct epithelial action on the proximal convoluted tubule. However, luminal dopamine antagonizes the stimulation in transport produced by norepinephrine. These studies suggest that luminal dopamine may play a role to modulate sodium transport in the presence of renal nerve activity.

Fig. 1

Effect of 10⁻⁵ m bath (A) and luminal (B) dopamine on proximal convoluted tubule volume absorption (J_v).

Fig. 2

Effect of 10⁻⁶ m bath norepinephrine and 10⁻⁵ m luminal dopamine in the presence of 10⁻⁶ M bath norepinephrine on (A) proximal convoluted tubule volume absorption (J_V) and (B) transepithelial potential difference (PD). *P ≤ 0.01 versus previous period; ⁺P > 0.05 versus revious period.

Fig. 3

Effect of 10⁻⁵ M bath dopamine in the presence of 10⁻⁶ M bath norepinephrine on volume absorption (A) and transepithelial potential difference (B).

Fig. 4

Effect of 10⁻⁶ M bath norepinephrine and 10⁻⁵ M luminal fenoldopam in the presence of 10⁻⁶ M bath norepinephrine on proximal convoluted tubule volume absorption (A) and transepithelial potential difference (B). *P < 0.01; ⁺P < 0.05.

Fig. 5

Effect of 10⁻⁵ M luminal dopamine in the presence of 10⁻⁵ M luminal SCH 23390 and 10⁻⁶ M bath norepinephrine on volume absorption (A) and transepithelial potential difference (B).

Fig. 6

Effect of 10⁻⁶ m bath norepinephrine and 10⁻⁵ m luminal quinpirole in the presence of 10⁻⁶ m bath norepinephrine on volume absorption (A) and transepithelial potential difference (B). *P < 0.05