Persistent defective coupling of dopamine-1 receptors to G proteins after solubilization from kidney proximal tubules of hypertensive rats.

Sidhu, Anita; Vachvanichsanong, Prayong; José, Pedro A.; Felder, Robin A.

doi:10.1172/jci115657

Cited by 38 publications

(22 citation statements)

References 33 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to its role in maintaining sodium homeostasis under normal conditions (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), defects in the renal paracrine/ autocrine DA axis have been demonstrated and postulated to contribute to certain forms of polygenic hypertension in both rodents (77)(78)(79)(80)(81)(82)(83)(84)(85)(86) and humans (87)(88)(89)(90)(91)(92). In the proximal tubule where 50 -60% of NaCl and water is reabsorbed, DA inhibits the basolateral membrane Na ϩ ,K ϩ -ATPase (34 -38), which is the primary driving force for transepithelial Na ϩ absorption.…”

Section: Discussionmentioning

confidence: 99%

Dopamine Acutely Stimulates Na+/H+Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles

Hu¹,

Fan²,

Crowder³

et al. 2001

Journal of Biological Chemistry

138

167

View full text Add to dashboard Cite

Extracellular fluid volume and to a certain extent blood pressure in mammals are determined by the balance between sodium intake and renal sodium excretion (1, 2). As regulator of sodium excretion, the intrarenal autocrine-paracrine dopamine (DA) 1 system assumes far greater importance than circulating endocrine or neurogenic dopamine (3-6). DA is produced in the proximal tubule via decarboxylation of its precursor L-dihydroxyphenylalanine derived from the plasma and glomerular filtrate (7-9) and is then secreted into the tubular lumen where it exerts its effects on multiple nephron segments, which cumulates in inhibition of tubular sodium absorption and natriuresis. Renal DA synthesis and excretion are increased by increased dietary salt and an intravenous saline load (10 -13), and blockade of DA synthesis or DA receptor significantly blunts the natriuretic response (14 -18). Quantitatively, the most significant inhibition of sodium transport occurs in the proximal tubule. DA inhibits proximal tubule sodium absorption partially by hemodynamic alterations (19 -22), but the major effect is directly on the tubule epithelium (23-26) via inhibition of two principal sodium transporters: the apical membrane Na ϩ /K ϩ exchanger (NHE3) (27-33) and the basolateral Na ϩ ,K ϩ -ATPase (34 -38). These effects are mediated by the DA receptor where five molecular isoforms (DR 1 -like receptors: DR 1 and DR 5 , and DR 2 -like receptors DR 2 , DR 3 , and DR 4 ) have been identified to date; all five isoforms are known to be present in the renal tubular epithelium (39 -43).Previous studies in isolated apical membrane vesicles have shown that DA inhibits proximal tubule apical membrane Na ϩ /H ϩ exchange activity mainly via DR 1 -like receptors (25-28, 30, 31, 33) through both PKA-dependent and PKA-independent mechanisms (27, 31). The Na ϩ /H ϩ exchanger on the apical membrane of the renal proximal tubule is encoded by NHE3 (44 -46), one of the seven members of the NHE gene family (47). We have shown in opossum kidney (OK) cells that the DA 1 -like and DA 2 -like receptors have synergistic actions on NHE3 activity and that inhibition of NHE3 activity by DA is accompanied by complex changes in NHE3 phosphorylation and dephosphorylation (33). However, the mechanisms by which DA acutely reduces NHE3 activity have not been examined. Redistribution of NHE3 transporters has been shown to mediate regulation of NHE3 activity in intact kidney (48 -54), in cultured renal epithelial cells (55,56), and in transfected fibroblasts (57-64). In addition, although NHE phosphorylation has been associated with changes in NHE3 activity (52,(65)(66)(67)(68), and phosphorylation appears to be functionally important for regulation of NHE3 activity by pharmacologic activators of protein kinases in transfected fibroblasts (65-67), the physiologic significance of NHE3 phosphorylation is still undetermined. In this paper we characterize one mechanism by which DA acutely inhibits NHE3: the internalization of NHE3 secondary to PKA-mediated NHE3 phosphorylatio...

show abstract

Section: Discussionmentioning

confidence: 99%

Dopamine Acutely Stimulates Na+/H+Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles

Hu¹,

Fan²,

Crowder³

et al. 2001

Journal of Biological Chemistry

138

167

View full text Add to dashboard Cite

show abstract

“…In two experimental models of hypertension, spontaneously hypertensive rats (SHR) and Dahl salt sensitive rats, defective coupling of dopamine to adenylate cyclase activation has been noted (49)(50)(51)(52)(53). In hypertensive humans, both defective renal dopamine production in response to salt loading and decreased proximal tubule responsiveness to dopamine have also been reported (54).…”

Section: Discussionmentioning

confidence: 99%

Dopamine decreases expression of type-1 angiotensin II receptors in renal proximal tubule.

Cheng¹,

Becker²,

Harris³

1996

J. Clin. Invest.

View full text Add to dashboard Cite

Systemic and/or locally produced angiotensin II stimulates salt and water reabsorption in the renal proximal tubule. In vivo, dopamine (DA) may serve as a counterregulatory hormone to angiotensin II's acute actions on the proximal tubule. We examined whether dopamine modulates AT 1 receptor expression in cultured proximal tubule cells (RPTC) expressing DA 1 receptors. Dopamine decreased basal RPTC AT 1 receptor mRNA levels by 67 Ϯ 7% ( n ϭ 10; P Ͻ 0.005) and decreased 125 I-angiotensin II binding by 41 Ϯ 7% ( n ϭ 4; P Ͻ 0.05). The DA 1 -specific agonist, SKF38393 decreased basal AT 1 receptor mRNA levels (65 Ϯ 5% inhibition; n ϭ 5; P Ͻ 0.025), and the DA 1 -specific antagonist, SCH23390 reversed dopamine's inhibition of AT 1 receptor mRNA expression (24 Ϯ 10% inhibition; n ϭ 8; NS) and angiotensin II binding (5 Ϯ 15%; n ϭ 4; NS). DA 2 -specific antagonists were ineffective. In rats given L-DOPA in the drinking water for 5 d, there were decreases in both proximal tubule AT 1 receptor mRNA expression (80 Ϯ 5%; n ϭ 6; P Ͻ 0.005) and specific

show abstract

“…83,89,90 We and others have performed extensive studies to investigate the site(s) of defect in the D 1 -like receptor system in the SHR. 4,39,[91][92][93] Because proximal tubular dopamine receptors (D 1 -like receptors) contribute to 60% of the sodium excretion under acute volume expansion, a phenomenon that is impaired in SHR, studies have been conducted on the D 1 -like receptor system in the proximal tubules to investigate the site of impairment. In 1989, Kinoshita et al 4 reported that D 1 -like receptor agonists stimulated adenylyl cyclase activity to a lesser extent in the proximal tubules of SHR compared with normotensive WKY.…”

Section: Spontaneously Hypertensive Ratsmentioning

confidence: 99%

Renal Dopamine Receptor Function in Hypertension

1998

View full text Add to dashboard Cite

Abstract-Dopamine plays an important role in the regulation of renal sodium excretion. The synthesis of dopamine and the presence of dopamine receptor subtypes (D 1A , D 1B as D 1 -like and D 2 , and D 3 as D 2 -like) have been shown within the kidney. The activation of D 1 -like receptors located on the proximal tubules causes inhibition of tubular sodium reabsorption by inhibiting Na,H-exchanger and Na,K-ATPase activity. The D 1 -like receptors are linked to the multiple cellular signaling systems (namely, adenylyl cyclase, phospholipase C, and phospholipase A 2 ) in the different regions of the nephron. Defective renal dopamine production and/or dopamine receptor function have been reported in human primary hypertension as well as in genetic models of animal hypertension. There may be a primary defect in D 1 -like receptors and an altered signaling system in the proximal tubules that lead to reduced dopamine-mediated effects on renal sodium excretion in hypertension. Recently, it has been shown in animal models that the disruption of either D 1A or D 3 receptors at the gene level causes hypertension in mice. Dopamine and dopamine receptor agonists also provide therapeutic potential in treatment of various cardiovascular pathological conditions, including hypertension. However, because of the poor bioavailability of the currently available compounds, the use of D 1 -like agonists is limited to the management of patients with severe hypertension when a rapid reduction of blood pressure is clinically indicated and in acute management of patients with heart failure. In conclusion, there is convincing evidence that dopamine and dopamine receptors play an important role in regulation of renal function, suggesting that a defective dopamine receptor/signaling system may contribute to the development and maintenance of hypertension. Further studies need to be directed toward establishing a direct correlation between defective dopamine receptor gene in the kidney and development of hypertension. Subsequently, it may be possible to use a therapeutic approach to correct the defect in dopamine receptor gene causing the hypertension. (Hypertension. 1998;32:187-197.)Key Words: dopamine Ⅲ receptors, dopamine Ⅲ kidney tubules, proximal Ⅲ kidney Ⅲ hypertension, renal D opamine is known to play an important role in the control of renal sodium excretion. Specific receptors for dopamine have been identified in various regions of the nephron, and it is reported that dopamine is synthesized within the renal proximal tubules. Endogenously produced dopamine, as well as exogenously administered dopamine, exerts pronounced effects on renal function. There are reports suggesting that a defect in renal dopamine receptor function and/or dopamine production may play a role in the pathogenesis of hypertension. For example, reduced urinary dopamine/ sodium excretion is reported in some forms of human primary hypertension. [1][2][3] It is reported that a defect in dopamine receptor-G protein coupling and alterations in the signaling component...

show abstract

Persistent defective coupling of dopamine-1 receptors to G proteins after solubilization from kidney proximal tubules of hypertensive rats.

Cited by 38 publications

References 33 publications

Dopamine Acutely Stimulates Na+/H+Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles

Dopamine Acutely Stimulates Na+/H+Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles

Dopamine decreases expression of type-1 angiotensin II receptors in renal proximal tubule.

Renal Dopamine Receptor Function in Hypertension

Contact Info

Product

Resources

About