Dopamine decreases fluid reabsorption in straight portions of rabbit proximal tubule

Abstract

The effects of DA and DA blockers on fluid transport, transepithelial potential difference (PD), and Na fluxes were studied in straight portions of the rabbit proximal tubule by the technique of microperfusion in vitro. DA (10(-6) M) added to the bath (rabbit serum) produced a significant decrease in fluid reabsorption (Jv, nl.min-2.mm-1) from 0.53 +/- 0.05 to 0.19 +/- 0.06 (n = 7, P less than 0.005). PD decreased from -2.7 +/- 0.5 to -1.2 +/- 0.4 mV (P less than 0.01). Drugs active on DA receptors were used to characterize the action of dopamine. Haloperidol (10(-8) M), lisuride (1.5 X 10(-9) M), and metoclopramide (10(-7) M) did not modify Jv by themselves but prevented the action of dopamine. Agonists of DA, Epinine and A 6,7 DTN, produced smaller or shorter decreases in Jv. A 6,7 DTN was active in the presence of alpha- and beta-adrenergic blockers. The serotonin antagonist methysergide decreases Jv by itself by 15%; in its presence DA was not effective. The effect of DA was accompanied by reductions of net Na flux and unidirectional lumen-to-bath and bath-to-lumen Na fluxes by approximately 25%. It is concluded that DA exerts a direct inhibitory effect on fluid transport by the pars recta. The evidence for the existence of DA receptor sites is not conclusive. The mechanism of action is uncertain, but an impairment of transcellular salt transport can be suggested.

Augmentation of renal blood flow and sodium excretion in hypertensive patients during blood pressure reduction by intravenous administration of the dopamine1 agonist fenoldopam.

“…Fourth, and most controversial, it is possible that fenoldopam exerts a direct effect on the renal tubules to prevent reabsorption of sodium. Microperfusion studies have shown that DA inhibits sodium transport in the pars recta of the rabbit proximal tubule, 22 and evidence has been presented to suggest that DA1 receptors are located on proximal tubular cells.23 This study does not allow us to distinguish between these possible mechanisms; however, the increase in Cc, + CH20 index suggests that fenoldopam causes a substantial reduction in the reabsorption of sodium in the proximal tubule. Changes in activity of the renin-angiotensinaldosterone system cannot be implicated.…”

Activation of protein kinase A acutely inhibits and phosphorylates Na/H exchanger NHE-3.

“…In the renal proximal tubule, adrenergic agonists (32-34), parathyroid hormone (PTH) (21,23,35), dopamine (20,36), angiotensin II (37)(38)(39), and endothelin (40,41) all regulate proximal tubule NaCl and/or NaHCO3 absorption, in part via modulation of apical membrane Na/H exchanger activity. For hormones such as dopamine and PTH, PKA activation is presumed to play a major role in mediating inhibition of Na/H exchanger activity (21-23, 35, 42).…”

The effect of lithium on the renal response to the dopamine prodrug gludopa in normal man.

“…Early in vivo studies suggested that dopamine may also exert specific effects on tubular salt handling (McGiff & Bums, 1967) and this question has more recently been addressed by in vitro tubular preparation techniques. Dopamine receptors have been identified on proximal tubular cells (Felder et al, 1984) and Bello-Reus et al (1982) . Dopamine stimulates cAMP synthesis in the rat kidney particulate preparation (Nakajima et al, 1977) and an increase in urine cAMP has been measured after dopamine infusion in man (Vlachoyannis et al, 1976).…”