Ontogenic aspects of D1 receptor coupling to G proteins and regulation of rat jejunal Na+, K+ ATPase activity and electrolyte transport

Vieira-Coelho, Maria Augusta; Soares-da-Silva, Patrı́cio

doi:10.1038/sj.bjp.0703065

Cited by 22 publications

(23 citation statements)

References 32 publications

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“…38 In intestinal cells, however, GRK6, rather than GRK4, regulates D 1 R function, 39 which is different from that observed in the kidney. 16,21 …”

Section: Physiological Role Of Grk4mentioning

confidence: 62%

“…The D 1 R also plays a role in sodium balance by inhibition of Na ϩ -K ϩ -ATPase activity in jejunal cells 38 ; dopamine fails to inhibit Na ϩ -K ϩ -ATPase activity in jejunal epithelial cells from SHRs. 38 In intestinal cells, however, GRK6, rather than GRK4, regulates D 1 R function, 39 which is different from that observed in the kidney.…”

Section: Physiological Role Of Grk4mentioning

confidence: 99%

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G Protein–Coupled Receptor Kinase 4

Zeng

Villar²,

Eisner³

et al. 2008

Hypertension

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N early 30% of middle-aged Americans have hypertension, but the prevalence is higher in non-Hispanic blacks and individuals Ͼ60 years of age (65%). 1 There is a direct and quantitative relationship between higher blood pressure values and mortality. Although 30% to 50% is thought to be heritable, the genetic cause(s) of essential hypertension has been difficult to identify. More than 1 gene is undoubtedly involved, because Mendelian dominant and recessive traits are not readily discernible in hypertensive subjects, except in those with monogenic forms of hypertension. Moreover, in any hypertensive individual, risk-predisposing genes are engaged in a complex network of gene-gene and geneenvironment interactions. 2,3 The kidney plays a major role in the long-term regulation of blood pressure, and abnormal sodium chloride metabolism is frequently encountered in hypertension. Therefore, many studies have focused on the abnormal renal handling of sodium chloride in the pathogenesis of essential hypertension. 2,4 Approximately 50% of subjects with essential hypertension are sodium chloride sensitive. 5 Indeed, humans with salt-sensitive hypertension have increased sodium transport in the renal proximal tubule and medullary thick ascending limb, although distal tubular mechanisms may also be involved. 6 The sodium retention in hypertension is because of enhanced sodium transport, per se, and/or a failure to respond appropriately to signals that decrease sodium transport. Sodium transport is regulated by natriuretic and antinatriuretic hormones and humoral agents, such as dopamine and angiotensin, which exert their effects via G protein-coupled receptors (GPCRs). Activation of certain postjunctional dopamine receptor subtypes (D 1 R, D 3 R, D 4 R, and D 5 R) and the angiotensin type 2 receptor inhibit, whereas activation of the postjunctional D 2 R and angiotensin type 1 receptor (AT 1 R) increase sodium transport. 2,7 GPCR Kinase FamilyThe GPCR kinases (GRKs) are a 7-member family of serine/threonine protein kinases characterized by their ability to phosphorylate or modify and desensitize agonist-occupied cell surface membrane GPCRs. GRKs 1 and 7 belong to the rhodopsin family; GRKs 2 and 3 belong to the ␤-adrenergic receptor kinase family, and GRKs 4, 5, and 6 belong to the GRK4 family (Table 1). GRKs 1 and 7 are expressed exclusively in rods and cones, respectively, in the retina. GRKs 2, 3, 5, and 6 are ubiquitously expressed, whereas GRK4 expression is limited (see below). 8 Overexpression of GRK2, GRK3, and especially GRK5 in human embryonic kidney cells desensitizes the D 1 R. 9 GRK activity and GRK2 expression are increased in lymphocytes of patients with essential hypertension and spontaneously hypertensive rats (SHRs). 10 Overexpression of GRK2 in vascular smooth muscles in mice produces hypertension and impairs the vasodilatory action of ␤-adrenergic receptors. 11 The vasoconstrictor response to angiotensin II is also impaired in these mice, which is at odds with the increased reactivity and sensitivity to an...

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“…38 In intestinal cells, however, GRK6, rather than GRK4, regulates D 1 R function, 39 which is different from that observed in the kidney. 16,21 …”

Section: Physiological Role Of Grk4mentioning

confidence: 62%

Section: Physiological Role Of Grk4mentioning

confidence: 99%

G Protein–Coupled Receptor Kinase 4

Zeng

Villar²,

Eisner³

et al. 2008

Hypertension

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show abstract

“…Activation of dopamine D 1 -like receptors in jejunal cells markedly inhibited Na + -K + -ATPase activity however, this effect was observed in young but not in adult rats [17][18][19]. The absence of dopamine effects in adult jejunal cells may be explained by regulatory mechanisms that modulate signaling by G protein-coupled receptors, such as agonist-induced desensitization of receptors.…”

mentioning

confidence: 79%

Dopamine D1-like Receptor-Mediated Inhibition of Cl-/HCO3- Exchanger Activity in Rat Intestinal Epithelial IEC-6 Cells is Regulated by G Protein-Coupled Receptor Kinase 6 (GRK 6)

Fraga

Luo

José

et al. 2006

Cell Physiol Biochem

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The present study investigated the effect of dopamine D₁-like receptor stimulation on the Cl^-/HCO₃^- exchange activity in rat intestinal epithelial IEC-6 cells. The Cl^-/HCO₃^- exchange activity was found to be a chloride-dependent, DIDS-sensitive and niflumate-insensitive process. The presence of the SLC26A6 anion exchanger was detected by both RT-PCR and immunoblotting analysis in IEC-6 cells, in which three different small interfering RNAs (siRNAs) targeting SLC26A6 markedly inhibited Cl^-/HCO₃^- exchange. Activation of dopamine D₁-like receptors with SKF 38393 inhibited Cl^-/HCO₃^- exchanger activity, this being antagonized by the D₁ selective antagonist SKF 83566. However, effects of SKF 38393 were maximal at 5 min of exposure to the agonist and rapidly diminished with no effect at 15 min, suggestive of agonist-induced desensitization of D₁-like receptors. Pretreatment of cells with heparin, a non-selective inhibitor of G protein-coupled receptor kinases (GRKs), prevented the observed attenuation of SKF 38393-induced inhibition of Cl^-/HCO₃^- exchange. Overnight pretreatment with anti-GRK6A and anti-GRK6B, but not with anti-GRK4 antibodies, prevented the loss of SKF 38393-mediated effects. Both PKA and PKC signaling pathways participate in SKF 38393-mediated inhibition of Cl^-/HCO₃^- exchange. These findings suggest that SLC26A6 is at least one of the anion exchanger’s family members responsible for Cl^-/HCO₃^- exchange in IEC-6 cells. Dopamine D₁ receptors in IEC-6 rapidly desensitize to D₁-like agonist stimulation and GRK 6, but not GRK 4, appear to be involved in agonist-mediated responsiveness and desensitization.

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“…This difference may explain the failure of DA to inhibit intestinal NKA activity in adult rats (66). Furthermore, the uninephrectomised and three-quarter nephrectomised rats (3/4nx rats, a model of chronic renal insufficiency) present DA-sensitive enhanced natriuresis.…”

Section: Da Receptor-mediated Regulation Of Nkamentioning

confidence: 99%

Crosstalk between dopamine receptors and the Na+/K+-ATPase (Review)

Zhang

Liang³

et al. 2013

Molecular Medicine Reports

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Abstract. Dopamine (DA) receptors, which belong to the G protein-coupled receptor family, are the target of ~50% of all modern medicinal drugs and constitute a large and diverse class of proteins whose primary function is to transduce extracellular stimuli into intracellular signals. Na + /K + -ATPase (NKA) is ubiquitous and crucial for the maintenance of intracellular ion homeostasis and excitability. Furthermore, it plays a critical role in diverse effects, including clinical cardiotonic and cardioprotective effects, ischemic preconditioning in the brain, natriuresis, lung edema clearance and other processes. NKA regulation is of physiological and pharmacological importance and has species-and tissue-specific variations. The activation of DA receptors regulates NKA expression/activity and trafficking in various tissues and cells, for example in the kidney, lung, intestine, brain, non-pigmented ciliary epithelium and the vascular bed. DA receptor-mediated regulation of NKA mediates a diverse range of cellular responses and includes endocytosis/exocytosis, phosphorylation/dephosphorylation of the α subunit of NKA and multiple signaling pathways, including phosphatidylinositol (PI)-phospholipase C/protein kinase (PK) C, cAMP/PKA, PI3K, adaptor protein 2, tyrosine phosphatase and mitogen-activated protein kinase/extracellular signal-regulated protein kinase. Furthermore, in brain and HEK293T cells, D 1 and D 2 receptors exist in a complex with NKA. Among D 1 and D 2 receptors and NKA, regulations are reciprocal, which leads to crosstalk between DA receptors and NKA. In the present study, the current understanding of signaling mechanisms responsible for the crosstalk between DA receptors and NKA, as well as with specific consequent functions, is reviewed.

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Ontogenic aspects of D₁ receptor coupling to G proteins and regulation of rat jejunal Na⁺, K⁺ ATPase activity and electrolyte transport

Cited by 22 publications

References 32 publications

G Protein–Coupled Receptor Kinase 4

G Protein–Coupled Receptor Kinase 4

Dopamine D<sub>1</sub>-like Receptor-Mediated Inhibition of Cl<sup>-</sup>/HCO<sub>3</sub><sup>-</sup> Exchanger Activity in Rat Intestinal Epithelial IEC-6 Cells is Regulated by G Protein-Coupled Receptor Kinase 6 (GRK 6)

Crosstalk between dopamine receptors and the Na+/K+-ATPase (Review)

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