Biphasic Regulation of Na
 +
 -HCO
 3
 −
 Cotransporter by Angiotensin II Type 1A Receptor

Horita, Shoko; Zheng, Yanan; Hara, Chiaki; Yamada, Hideomi; Kunimi, Motoei; Taniguchi, Shigeo; Uwatoko, Shu; Sugaya, Takeshi; Goto, Atsuo; Fujita, Toshiro; Seki, George

doi:10.1161/01.hyp.0000036449.70110.de

Cited by 53 publications

(73 citation statements)

References 43 publications

(60 reference statements)

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“…This preparation is suitable for the identification of biphasic effects of Ang II on NBCe1 mediated through basolateral AT 1 receptors. 11,15,17,19 The basal NBCe1 activity (60.062.3 mM/min, n=70) determined from 22 persons ages 59.362.0 years was lower than the activity (82.262.2 mM/min, n=41) from 11 mice ages 9.160.8 weeks. Unlike Ang II in mouse or rabbit PTs, [9][10][11]17 Ang II in human PTs induced a dose-dependent marked stimulation of the NBCe1 activity ( Figure 1A 11,20 The stimulation of NBCe1 by Ang II was largely suppressed by a specific AT 1 inhibitor valsartan ( Figure 1B) and completely suppressed by an mitogen-activated protein kinase/ERK (MEK) inhibitor PD98059 ( Figure 1C), indicating that the AT 1 /MEK/ERK pathway mediates the stimulatory effect of Ang II.…”

Section: Resultsmentioning

confidence: 96%

“…7,17 Both arachidonic acid and 5,6-EET failed to inhibit the human NBCe1 activity (Supplemental Figure 1), although they did inhibit the mouse NBCe1 activity as reported. 11,17 To further clarify the mechanism(s) underlying the different modes of PT transport regulation by Ang II, we next examined the role of the NO/cGMP pathway, which might also mediate the inhibitory effect of Ang II in the other species. 12,18 As previously reported, 11,17 Ang II had biphasic effects on NBCe1 activity in mouse PTs (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…5 Ang II regulates the major PT sodium transporters the apical Na + /H + exchanger isoform 3 (NHE3), the basolateral Na + -HCO 3 2 cotransporter (NBCe1), and the basolateral Na + /K + ATPase in the biphasic manner. [7][8][9][10][11][12] Although controversial results had been reported of the receptor subtype(s) mediating the biphasic effects of Ang II, 13,14 the studies using isolated PTs obtained from AT 1A knockout (KO) mice have established that AT 1A mediates both the stimulatory and inhibitory effects of Ang II. 11,15 The stimulation by Ang II has been attributed to the activation of protein kinase C and/or the decrease in the intracellular cAMP concentration, resulting in the activation of extracellular signal-regulated kinase (ERK) pathway.…”

mentioning

confidence: 99%

“…[7][8][9][10][11][12] Although controversial results had been reported of the receptor subtype(s) mediating the biphasic effects of Ang II, 13,14 the studies using isolated PTs obtained from AT 1A knockout (KO) mice have established that AT 1A mediates both the stimulatory and inhibitory effects of Ang II. 11,15 The stimulation by Ang II has been attributed to the activation of protein kinase C and/or the decrease in the intracellular cAMP concentration, resulting in the activation of extracellular signal-regulated kinase (ERK) pathway. [16][17][18] However, the inhibition by Ang II has been attributed to the activation of the phospholipase A 2 /arachidonic acid/5,6-epoxyeicosatrienoic acid (EET) pathway and/or the nitric oxide (NO)/guanosine 39,59-cyclic monophosphate (cGMP) pathway.…”

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confidence: 99%

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Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate Pathway

Shirai¹,

Horita²,

Nakamura³

et al. 2014

Journal of the American Society of Nephrology

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Stimulation of renal proximal tubule (PT) transport by angiotensin II (Ang II) is critical for regulation of BP. Notably, in rats, mice, and rabbits, the regulation of PT sodium transport by Ang II is biphasic: transport is stimulated by picomolar to nanomolar concentrations of Ang II but inhibited by nanomolar to micromolar concentrations of Ang II. However, little is known about the effects of Ang II on human PT transport. By functional analysis with isolated PTs obtained from nephrectomy surgery, we found that Ang II induces a dose-dependent profound stimulation of human PT transport by type 1 Ang II receptor (AT 1 )-dependent phosphorylation of extracellular signal-regulated kinase (ERK). In PTs of wild-type mice, the nitric oxide (NO) /cGMP/cGMP-dependent kinase II (cGKII) pathway mediated the inhibitory effect of Ang II. In PTs of cGKII-deficient mice, the inhibitory effect of Ang II was lost, but activation of the NO/cGMP pathway failed to phosphorylate ERK. Conversely, in human PTs, the NO/cGMP pathway mediated the stimulatory effect of Ang II by phosphorylating ERK independently of cGKII. These contrasting responses to the NO/cGMP pathway may largely explain the different modes of PT transport regulation by Ang II, and the unopposed marked stimulation of PT transport by high intrarenal concentrations of Ang II may be an important factor in the pathogenesis of human hypertension. Additionally, the previously unrecognized stimulatory effect of the NO/cGMP pathway on PT transport may represent a human-specific therapeutic target in hypertension.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate Pathway

Shirai¹,

Horita²,

Nakamura³

et al. 2014

Journal of the American Society of Nephrology

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“…Although controversial data have been reported concerning the receptor subtype(s) that are responsible for the biphasic effects of ANG II on proximal tubular transport [87,88], some studies have clearly indicated that both luminal and basolateral AT1A receptors mediate the biphasic effects of Ang II on proximal transport [89][90][91]. It has been shown that at physiological concentrations, binding between ANG II and the AT1 receptor induces the rapid activation of PLC, which results in the release of IP3 and DAG, which are themselves involved in slightly increasing [Ca 2+ ]i by mobilizing Ca 2+ from intracellular storage and by activating PKC, respectively [92][93][94].…”

Section: Dose-dependent Biphasic Effects Of Ang II In the Proximal Tumentioning

confidence: 99%

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

Mello-Aires¹,

Dellova²,

Castelo‐Branco³

et al. 2017

Nephrol Renal Dis

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This article reviews the main body of knowledge regarding NHE1 and NHE3 exchangers and their interaction with Angiotensin II, Angiotensin-(1-7), Aldosterone and Arginine Vasopressin, particularly their renal actions. This work addresses the biphasic effects of different hormonal doses on NHE1 or NHE3 in proximal tubule in Wistar, SHR (hypertensives) and their control WKY (normotensives) rats or MDCK cells (which share similarities with the collecting duct). The hormones were applied alone, with their inhibitors or plus agents that change the [Ca 2+ ]i. The data are compatible with hormonal stimulation of these exchangers by increases of [Ca 2+ ]i in lower range, and inhibition at high [Ca 2+ ]i. In MDCK cells and Wistar rats, low doses of ANG II, ALDO or AVP stimulated the exchangers, while high doses inhibited them. ANG-(1-7), in Wistar or WKY rats has inverse, dose-dependent effects. In SHR rats, the biphasic effects of ANG-(1-7) were similar to the effects of ANG II, ALDO or AVP in Wistar rats. The interactions between these effects may represent a mechanism that regulates extracellular volume. In hypertensives animals, a high plasma level of ANG-(1-7) inhibited NHE3 in the proximal tubule, which mitigated hypertension. Figure 6 shows a schematic model to describe these biphasic hormonal effects.

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Proximal Nephron

Zhuo,

2013

Comprehensive Physiology

167

140

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The kidney plays a fundamental role in maintaining body salt and fluid balance and blood pressure homeostasis through the actions of its proximal and distal tubular segments of nephrons. However, proximal tubules are well recognized to exert a more prominent role than distal counterparts. Proximal tubules are responsible for reabsorbing approximately 65% of filtered load and most, if not all, of filtered amino acids, glucose, solutes, and low molecular weight proteins. Proximal tubules also play a key role in regulating acid-base balance by reabsorbing approximately 80% of filtered bicarbonate. The purpose of this review article is to provide a comprehensive overview of new insights and perspectives into current understanding of proximal tubules of nephrons, with an emphasis on the ultrastructure, molecular biology, cellular and integrative physiology, and the underlying signaling transduction mechanisms. The review is divided into three closely related sections. The first section focuses on the classification of nephrons and recent perspectives on the potential role of nephron numbers in human health and diseases. The second section reviews recent research on the structural and biochemical basis of proximal tubular function. The final section provides a comprehensive overview of new insights and perspectives in the physiological regulation of proximal tubular transport by vasoactive hormones. In the latter section, attention is particularly paid to new insights and perspectives learnt from recent cloning of transporters, development of transgenic animals with knockout or knockin of a particular gene of interest, and mapping of signaling pathways using microarrays and/or physiological proteomic approaches.

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Biphasic Regulation of Na ⁺ -HCO ₃ ⁻ Cotransporter by Angiotensin II Type 1A Receptor

Cited by 53 publications

References 43 publications

Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate Pathway

Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate Pathway

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

Proximal Nephron

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Biphasic Regulation of Na + -HCO 3 − Cotransporter by Angiotensin II Type 1A Receptor

Cited by 53 publications

References 43 publications

Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate Pathway

Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate Pathway

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

Proximal Nephron

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Product

Resources

About

Biphasic Regulation of Na ⁺ -HCO ₃ ⁻ Cotransporter by Angiotensin II Type 1A Receptor