Anatomical distribution and function of dopamine receptors in the kidney

Abstract

Dopamine receptors of DA-1 and DA-2 subtypes are localized in various regions within the kidney including the renal vasculature (DA-1) as well as sympathetic nerve terminals innervating the renal blood vessels (DA-2). More recent studies using receptor-ligand binding and receptor autoradiography have shown that DA-1 receptors are localized at both the luminal and basolateral membranes at the level of the proximal tubules. Activation of these DA-1 receptors by dopamine and by selective DA-1 receptor agonists results in natriuresis and diuresis. The cellular signaling mechanisms responsible for this response appear to be DA-1 receptor-induced activation of adenylate cyclase and phospholipase C, which via the generation of various intracellular messenger systems cause inhibition of Na(+)-H+ antiport (luminal) and Na+, K(+)-ATPase (basolateral), respectively. Both of these events consequently inhibit sodium reabsorption leading to natriuresis and diuresis. It is also known that dopamine can be synthesized within proximal tubular cells from L-dopa, which is taken up from the tubular lumen, and this locally produced dopamine plays an important role in the regulation of sodium excretion particularly during increases in sodium intake. Furthermore, a defect in the renal dopaminergic mechanism may be one of the pathogenic factors in certain forms of hypertension. Finally, whereas DA-1 receptor agonists are shown to be of therapeutic benefit in the treatment of hypertension, heart failure, and acute renal failure, some selective DA-2 receptor agonists are effective antihypertensive agents.

Aging, High Salt Intake, and Renal Dopaminergic Activity in Fischer 344 Rats

“…This suggestion is substantiated by the observation that renal tubular cells from old rats take up less exogenous L-DOPA. 2,18 The inability of old rats on an HS intake to increase urinary dopamine excretion may be related to the reduced uptake of L-DOPA by tubular cells. In fact, several groups have shown an association between renal delivery of sodium and the ability to form dopamine, 26,27 and in vitro studies have shown that L-DOPA uptake by renal epithelial cells is a sodium-dependent process.…”

“…1,2 At the level of the proximal tubule, the overall increase in sodium excretion produced by dopamine and D 1 receptor agonists results from inhibition of Na ϩ ,K ϩ -adenosine triphosphatase (Na ϩ ,K ϩ -ATPase) 3 and the Na ϩ /H ϩ exchanger. 4 Inhibition of Na ϩ ,K ϩ -ATPase by dopamine occurs via a phospholipase C-coupled protein kinase C-linked pathway.…”

Dopamine D4 Receptor Expression in Rat Kidney: Evidence for Pre- and Postjunctional Localization

“…I ncreasing evidence has emphasized the role of dopamine in the regulation of renal function (Lokhandwala and Amenta 1991;Cheung and Barrington 1996;Jose et al 1998). The renal effects of dopamine include the following: (a) active vasodilatation, mediated by dopamine receptors located in the smooth muscle of renal artery branches; (b) passive vasodilatation, caused by reduction of the sympathetic vasoconstrictor tone; and (c) diuresis and natriuresis.…”

“…Dopamine, acting as a paracrine/autocrine substance, is involved in the regulation of renal function during volume expansion. During moderate sodium loading (up to 10% of body weight), dopamine is responsible for more than 50% of sodium excreted (Lokhandwala and Amenta 1991;Cheung and Barrington 1996;Jose et al 1998). The renal actions of dopamine are mediated through their interaction with specific receptors belonging to the D1-like and D2-like superfamilies (Lokhandwala and Amenta 1991;Ricci et al 1991;Sibley and Monsma 1992;Gingrich and Caron 1993;Cheung and Barrington 1996;Jose et al 1998).…”

“…During moderate sodium loading (up to 10% of body weight), dopamine is responsible for more than 50% of sodium excreted (Lokhandwala and Amenta 1991;Cheung and Barrington 1996;Jose et al 1998). The renal actions of dopamine are mediated through their interaction with specific receptors belonging to the D1-like and D2-like superfamilies (Lokhandwala and Amenta 1991;Ricci et al 1991;Sibley and Monsma 1992;Gingrich and Caron 1993;Cheung and Barrington 1996;Jose et al 1998). Dopamine D1-like receptors, which include the D1 and, to a lesser extent, the D5 subtypes, are located in smooth muscle of intrarenal arteries and in tubules of the renal cortex (Amenta 1990(Amenta ,1997Lokhandwala and Amenta 1991;Ricci et al 1993;Cheung and Barrington 1996).…”