Angiotensin II-dependent proximal tubule sodium transport is mediated by cAMP modulation of phospholipase C

Schelling, Jeffrey R.; Singh, Harmeet; Marzec, Rochelle; Linas, Stuart L.

doi:10.1152/ajpcell.1994.267.5.c1239

Cited by 39 publications

(41 citation statements)

References 17 publications

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“…There is strong evidence that accumulation of cAMP in B type intercalated cells stimulates bicarbonate secretion (20)(21)(22). Accordingly, insofar as AII is associated with decreased proximal tubule adenylate cyclase activity (23), it is conceivable that this second messenger could play a role at the distal tubule site modulating bicarbonate transport. Two observations bear critically on this possibility.…”

Section: Discussionmentioning

confidence: 99%

Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Levine¹,

Iacovitti²,

Buckman³

et al. 1996

J. Clin. Invest.

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We have reported that overnight fasting stimulates bicarbonate reabsorption (J tCO2 ) in rat distal tubules. The present in vivo microperfusion studies evaluated the hypothesis that endogenous angiotensin II (AII) mediates this response. Rat late distal (LD) tubules were perfused at 8 nl/min in vivo with a hypotonic solution containing 28 mM bicarbonate. In overnight-fasted rats, LD J tCO2 was significantly higher than in normally fed rats (50 Ϯ 4 vs. 16 Ϯ 6 pmol/min и mm, P Ͻ 0.05). When overnight-fasted rats were salt-loaded, J tCO2 fell significantly (38 Ϯ 3 pmol/min и mm, P Ͻ 0.05). Conversely, in fed rats ingesting a zero-salt diet, J tCO2 increased threefold (45 Ϯ 5 pmol/min и mm, P Ͻ 0.05). Enalaprilat infusion (0.25 g/kg body wt, intravenously), in these zero-salt and overnight-fasted rats, reduced LD J tCO2 values to normal. Further, infusion of losartan (5 mg/kg body wt, intravenously), the specific AII AT 1 receptor blocker, reduced J tCO2 in overnight-fasted rats by two-thirds (16 Ϯ 4 pmol/min и mm, P Ͻ 0.05). Finally, we perfused 10 Ϫ 11 M AII intraluminally with and without 10 Ϫ 6 M losartan: AII increased J tCO2 to 45 Ϯ 6 pmol/min и mm, equal to the zero-salt flux. This was completely abrogated by simultaneous losartan perfusion. Therefore, these results suggest that AII is an in vivo stimulator of late distal tubule bicarbonate reabsorption. ( J. Clin. Invest. 1996. 97:120-125.)

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Section: Discussionmentioning

confidence: 99%

Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Levine¹,

Iacovitti²,

Buckman³

et al. 1996

J. Clin. Invest.

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“…ANG II regulates Ca 2ϩ reabsorption in both luminal and basolateral aspects of tubule membranes (4, 5, 13). In proximal tubule cells, intracellular Ca 2ϩ mobilization activates Ca 2ϩ -dependent intracellular signaling pathways, including those associated with ANG II-modulated Na ϩ and water reabsorption mechanisms (8,16,17,39,42).Active and passive transport mechanisms participate in Ca 2ϩ reabsorption in the proximal tubules (19,48). Concerning primary active transporters, there are two main Ca 2ϩ -ATPase subfamilies in proximal tubule cells, the sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA) and the plasma membrane Ca 2ϩ -ATPase (PMCA) (38).…”

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confidence: 99%

Exposure of luminal membranes of LLC-PK₁cells to ANG II induces dimerization of AT₁/AT₂receptors to activate SERCA and to promote Ca²⁺mobilization

Ferrão

Lara

Axelband

et al. 2012

American Journal of Physiology-Renal Physiology

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Using the PLC inhibitor U73122, PMA, and calphostin C, it was possible to demonstrate the involvement of a PLC¡DAG(PMA)¡PKC pathway in the stimulation of SERCA by ANG II with no effect on PMCA. We conclude that ANG II triggers SERCA activation via the luminal membrane, increasing the Ca 2ϩ stock in the reticulum to ensure a more efficient subsequent mobilization of Ca 2ϩ . This first report on the regulation of SERCA activity by ANG II shows a new mechanism for Ca 2ϩ homeostasis in renal cells and also for regulation of Ca 2ϩ -modulated fluid reabsorption in proximal tubules.luminal effect of ANG II; Ca 2ϩ sparks; proximal tubule Ca 2ϩ homeostasis; fluid reabsorption THE KIDNEY IS an essential organ in homeostasis and body fluid regulation. Its functions are modulated by different hormones and autacoids that act on hydroelectrolytic balance, extracellular volume, and blood pressure, such as angiotensin II (ANG II) (24). ANG II plays a crucial role in renal Ca 2ϩ handling, one of the main cell messengers (4, 5, 13, 51), which is involved in the fine tuning of fluid reabsorption in different segments of the nephron (17). Approximately 60% of the plasma Ca 2ϩ is filtered by the kidneys, 99% of which is reabsorbed (70% of it in the proximal tubules) (19). ANG II regulates Ca 2ϩ reabsorption in both luminal and basolateral aspects of tubule membranes (4, 5, 13). In proximal tubule cells, intracellular Ca 2ϩ mobilization activates Ca 2ϩ -dependent intracellular signaling pathways, including those associated with ANG II-modulated Na ϩ and water reabsorption mechanisms (8,16,17,39,42).Active and passive transport mechanisms participate in Ca 2ϩ reabsorption in the proximal tubules (19,48). Concerning primary active transporters, there are two main Ca 2ϩ -ATPase subfamilies in proximal tubule cells, the sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA) and the plasma membrane Ca 2ϩ -ATPase (PMCA) (38). These pumps control intracellular Ca 2ϩ concentration by regulating intracellular Ca 2ϩ stocks, fine-tuning cytosolic Ca 2ϩ activity in many cell types (12). Therefore, renal SERCA and PMCA are excellent targets for hormones, including ANG II and angiotensin-derived peptides (6). We found that picomolar ANG II inhibits PMCA activity via a PLC/protein kinase C (PKC) pathway triggered by the peptide binding to AT 1 R/AT 2 R heterodimers (4, 5). Micromolar ANG II is metabolized by peptidases associated with the basolateral membrane, generating Ang-(3-4) that reactivates PMCA (5, 6).Classically, ANG II was described to be formed only systemically. Different studies in the last two decades found that ANG II is formed in different tissues such as brain, heart, and adipose tissue (7,18,34) and, especially, in kidney, where local renin-angiotensin system was first described (10,20,25,26,28,50). Because of this local synthesis, ANG II levels are much higher in the kidney than in plasma (37, 43), being found in proximal tubule fluid in the nanomolar range (9,23,36,43). This tubular fluid ANG II is not only derived from the filtrate...

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“…Indeed, subcellular localization of 125 I-labeled Ang Ⅱ in the pig kidney indicates that Ang Ⅱ generation is predominantly extracellular, followed by AT1 receptor-mediated endocytosis leading to higher intracellular Ang Ⅱ levels [109] . In accord with this, internalization is seen to be important for AT1a receptor function in polarized proximal tubule epithelial cells, where apical AT1a receptor internalize before interaction with G proteins, which stimulates phospholipase C and cAMP to increase proximal tubule Na + reabsorption [110,111] . Within the kidney, cells from different segments can generate Ang Ⅱ or internalize Ang Ⅱ through the AT1 receptor [109][110][111] .…”

Section: Breaking Paradigmsmentioning

confidence: 69%

“…In accord with this, internalization is seen to be important for AT1a receptor function in polarized proximal tubule epithelial cells, where apical AT1a receptor internalize before interaction with G proteins, which stimulates phospholipase C and cAMP to increase proximal tubule Na + reabsorption [110,111] . Within the kidney, cells from different segments can generate Ang Ⅱ or internalize Ang Ⅱ through the AT1 receptor [109][110][111] . In vitro and in vivo studies showed that extracellular Ang Ⅱ accumulates within the kidney via AT1a receptor-mediated endocytosis [82,83,107] .…”

Section: Breaking Paradigmsmentioning

confidence: 69%

Renin-angiotensin system in the kidney: What is new?

Ferrão

Lara

Lowe

2014

WJN

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The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin Ⅱ (Ang Ⅱ) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang Ⅱ formation or even active Ang Ⅱ-derived peptides have now been described acting on Ang Ⅱ AT1 or AT2 receptors, or in receptors which have recently been cloned, such as Mas and AT4. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang Ⅱ formation. This in situ formation, especially in the kidney, increases Ang Ⅱ levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang Ⅱ effects, improves the development of new drugs for treating hypertension and cardiovascular diseases. Key words: Renin-angiotensin system; Angiotensin Ⅱ; Kidney; Hypertension treatment; Receptor Core tip: Activation of the angiotensin converting enzyme (ACE)/ Angiotensin Ⅱ (Ang Ⅱ)/AT1 axis leads to vasoconstriction, anti-diuresis, anti-natriuresis, release of aldosterone and anti-diuretic hormone, which can result in hypertension, renal and cardiovascular diseases. Inhibition of renin and ACE or blocking AT1 receptor is the most used therapies for heart failure and hypertension. Nevertheless, the discovery of local Ang Ⅱ synthesis, new Ang Ⅱ metabolites, receptors and axis of this system, makes possible the development of new drugs and strategies for renal and cardiovascular diseases treatment, such as activation of ACE2/Ang-(1-7)/ Mas axis, which presents opposite effects of AT1 activation by Ang Ⅱ.

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Angiotensin II-dependent proximal tubule sodium transport is mediated by cAMP modulation of phospholipase C

Cited by 39 publications

References 17 publications

Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Exposure of luminal membranes of LLC-PK₁cells to ANG II induces dimerization of AT₁/AT₂receptors to activate SERCA and to promote Ca²⁺mobilization

Renin-angiotensin system in the kidney: What is new?

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Angiotensin II-dependent proximal tubule sodium transport is mediated by cAMP modulation of phospholipase C

Cited by 39 publications

References 17 publications

Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Exposure of luminal membranes of LLC-PK1cells to ANG II induces dimerization of AT1/AT2receptors to activate SERCA and to promote Ca2+mobilization

Renin-angiotensin system in the kidney: What is new?

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Exposure of luminal membranes of LLC-PK₁cells to ANG II induces dimerization of AT₁/AT₂receptors to activate SERCA and to promote Ca²⁺mobilization