Renal Dopamine Receptors and Hypertension

Abstract

Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D(1) receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D(1) receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.

Inhibition of D 4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells

“…The D 4 receptor has abundant protein expression in the proximal tubule 3, 13. Previous studies show interactions between insulin and dopamine receptors.…”

“…Others also showed that the interactive role of cAMP regulatory element‐binding protein and Sp1 is regulated by calcium 42. As a D 2 ‐like receptor subtype, activation of D 4 receptor increases intracellular calcium concentration 3. The present study showed that the inhibitory effect of D 4 receptor on insulin receptor expression is blocked by a calcium‐channel blocker, withdrawal of calcium in the cell culture medium, or in the presence of IP3 receptor blocker, which blocks the calcium release from endoplasmic reticulum, indicating that calcium mobilization, including extracellular calcium influx and intracellular calcium release from the endoplasmic reticulum, is involved in the signaling pathway.…”

“…There are evidences indicating that insulin, through stimulation of Na + /H + exchange and Na + ‐K + ‐ATPase activities directly, increases volume absorption in renal proximal tubules 6. Dopamine is an endogenous catecholamine that modulates many cellular activities, including blood pressure and transmembrane ion transport 3. Dopamine receptors are classified into the D 1 ‐like and D 2 ‐like subtypes based on their structure and pharmacology.…”

“…Dopamine receptors are classified into the D 1 ‐like and D 2 ‐like subtypes based on their structure and pharmacology. D 1 ‐like receptors, comprised of D 1 and D 5 receptors, stimulate adenylyl cyclase activity, whereas D 2 ‐like receptors, comprised of D 2 , D 3 , and D 4 receptors, inhibit adenylyl cyclase activity, and regulate/modulate activity of several ion channels 3. Activation of D 1 ‐like or D 2 ‐like receptor induces natriuresis and diuresis 9…”

D3 dopamine receptor regulation of D5 receptor expression and function in renal proximal tubule cells

“…[4][5][6] Several studies have reported that an impaired renal dopaminergic system may contribute to the pathogenesis of hypertension. 7,8 Dopamine receptors expressed in mammals belong to the a group of the rhodopsin family of G protein-coupled receptors. The five mammalian dopamine receptor subtypes, identified by molecular cloning, differ in their primary structures, and have distinct affinities for dopamine receptor agonists and antagonists.…”