Angiotensin II stimulates ammoniagenesis in canine renal proximal tubule segments

1991 ◽  
Vol 260 (1) ◽  
pp. F19-F26 ◽  
Author(s):  
M. C. Chobanian ◽  
C. M. Julin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Glucose Production ◽  
Renal Proximal Tubule ◽  
Ang Ii ◽  
Ammonia Production ◽  
Proximal Tubule Segments ◽  
Dependent Pathway ◽  
Stimulation Of

To determine whether angiotensin II (ANG II) affects ammoniagenesis in renal proximal tubule, ammonia production was measured in suspensions of canine renal proximal tubule segments (PCT) incubated with L-glutamine and varying concentrations of ANG II. Ammonia production from PCT was significantly increased by 15.5 +/- 1.1% in the presence of ANG II (10(-6) M) at 2 h. Similarly, glucose production significantly increased by 10.0 +/- 0.9%. Half-maximal stimulation occurred at approximately 10(-9) M ANG II. Stimulation of ammonia production by ANG II was blocked in the presence of the ANG II antagonist, [Sar1-Ile8]ANG II (10(-6) M). Enhancement of ammonia production in PCT by ANG II occurred in acidotic and neutral media but not in alkalotic medium. When extracellular [Na+] = intracellular [Na+] ANG II significantly increased ammonia production in PCT. Absence of extracellular Ca2+ or addition of trifluoperazine or N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) (Ca2(+)-calmodulin-dependent pathway inhibitors) blocked the action of ANG II to enhance ammonia production. We conclude that ANG II stimulates ammonia and glucose production in canine renal PCT via a receptor-mediated signal. The action of ANG II on ammoniagenesis may be mediated by a calcium-calmodulin-dependent pathway. Stimulation of ammoniagenesis in vitro under normal and acidotic conditions may reflect a role in vivo for ANG II in the regulation of renal acid-base metabolism.

Growth hormone regulates ammoniagenesis in canine renal proximal tubule segments

1992 ◽  
Vol 262 (5) ◽  
pp. F878-F884 ◽  
Author(s):  
M. C. Chobanian ◽  
C. M. Julin ◽  
K. H. Molteni ◽  
P. C. Brazy
Keyword(s):  
Growth Hormone ◽  
Atpase Activity ◽  
Proximal Tubule ◽  
Human Growth ◽  
Glucose Production ◽  
Renal Proximal Tubule ◽  
Ammonia Production ◽  
Physiological Conditions ◽  
Dose Dependent ◽  
Proximal Tubule Segments

To determine whether growth hormone (GH) directly affects ammoniagenesis in the renal proximal tubule, ammonia production was measured in suspensions of isolated canine renal proximal tubule segments (IPTs) incubated with 2.5 mM L-glutamine and varying concentrations of human growth hormone (hGH). Ammonia production from IPTs significantly increased by nearly threefold in the presence of hGH (10(-6) M) at 60 min. This increase was dose dependent, with as little as 10(-9) M hGH significantly stimulating ammonia production. In addition, hGH enhanced glucose production when lactate, alanine, and succinate replaced L-glutamine as substrate. hGH significantly stimulated ammonia production when IPTs were incubated at alkalotic and neutral pH. The effect of hGH was lost at acidic pH. When hGH was added to IPTs incubated under Na(+)-equilibrated conditions, ammonia production was not different from control. hGH stimulated ouabain-sensitive Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity by 8.1 +/- 1.1% in basolateral membranes isolated from IPTs. hGH stimulation of proximal tubule ammonia production from L-glutamine occurs at physiological concentrations of hGH and when the extracellular-to-intracellular Na+ gradient favors L-glutamine transport. This effect is associated with an increase in basolateral Na(+)-K(+)-ATPase activity. The data suggest a role for hGH in the regulation of renal acid-base metabolism under physiological conditions in which increased net acid excretion is important.

Enhanced ammonia secretion by proximal tubules from mice receiving NH4Cl: role of angiotensin II

2002 ◽  
Vol 282 (3) ◽  
pp. F472-F477 ◽  
Author(s):  
Glenn T. Nagami ◽  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Ang Ii ◽  
Ammonia Production ◽  
Short Term ◽  
Adaptive Enhancement ◽  
And Control ◽  
Secretion Rates

Acidosis and angiotensin II (ANG II) stimulate ammonia production and transport by the proximal tubule. We examined the effect of short-term (18 h) in vivo acid loading with NH4Cl on ammonia production and secretion rates by mouse S2 proximal tubule segments microperfused in vitro with or without ANG II in the luminal microperfusion solution. S2 tubules from NH4Cl-treated mice displayed higher rates of luminal ammonia secretion compared with those from control mice. The adaptive increase in ammonia secretion in NH4Cl-treated mice was eliminated when losartan was coadministered in vivo with NH4Cl. Ammonia secretion rates from both NH4Cl-treated and control mice were largely inhibited by amiloride. Addition of ANG II to the microperfusion solution enhanced ammonia secretion and production rates to a greater extent in tubules from NH4Cl-treated mice compared with those from controls, and the stimulatory effects of ANG II were blocked by losartan. These results demonstrate that a short-term acid challenge induces an adaptive increase in ammonia secretion by the proximal tubule and suggest that ANG II plays an important role in the adaptive enhancement of ammonia secretion that is observed with short-term acid challenges.

scholarly journals Dietary fructose enhances angiotensin II-stimulated Na+ transport via activation of PKC-α in renal proximal tubules

2020 ◽  
Vol 318 (6) ◽  
pp. F1513-F1519
Author(s):  
Nianxin Yang ◽  
Nancy J. Hong ◽  
Jeffrey L. Garvin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Tap Water ◽  
Renal Proximal Tubule ◽  
Proximal Tubules ◽  
Control Group ◽  
Ang Ii ◽  
Dietary Fructose ◽  
Intracellular Ca ◽  
Pkc Β

Angiotensin II (ANG II) stimulates proximal nephron transport via activation of classical protein kinase C (PKC) isoforms. Acute fructose treatment stimulates PKC and dietary fructose enhances ANG II’s ability to stimulate Na+ transport, but the mechanisms are unclear. We hypothesized that dietary fructose enhances ANG II’s ability to stimulate renal proximal tubule Na+ reabsorption by augmenting PKC-α activation and increases in intracellular Ca2+. We measured total and isoform-specific PKC activity, basal and ANG II-stimulated oxygen consumption, a surrogate of Na+ reabsorption, and intracellular Ca2+ in proximal tubules from rats given either 20% fructose in their drinking water (fructose group) or tap water (control group). Total PKC activity was measured by ELISA. PKC-α, PKC-β, and PKC-γ activities were assessed by measuring particulate-to-soluble ratios. Intracelluar Ca2+ was measured using fura 2. ANG II stimulated total PKC activity by 53 ± 15% in the fructose group but not in the control group (−15 ± 11%, P < 0.002). ANG II stimulated PKC-α by 0.134 ± 0.026 but not in the control group (−0.002 ± 0.020, P < 0.002). ANG II increased PKC-γ activity by 0.008 ± 0.003 in the fructose group but not in the control group ( P < 0.046). ANG II did not stimulate PKC-β in either group. ANG II increased Na+ transport by 454 ± 87 nmol·min−1·mg protein−1 in fructose group, and the PKC-α/β inhibitor Gö6976 blocked this increase (−96 ± 205 nmol·min−1·mg protein−1, P < 0.045). ANG II increased intracellular Ca2+ by 148 ± 53 nM in the fructose group but only by 43 ± 10 nM in the control group ( P < 0.035). The intracellular Ca2+ chelator BAPTA blocked the ANG II-induced increase in Na+ transport in the fructose group. We concluded that dietary fructose enhances ANG II’s ability to stimulate renal proximal tubule Na+ reabsorption by augmenting PKC-α activation via elevated increases in intacellular Ca2+.

Effect of luminal angiotensin II on ammonia production and secretion by mouse proximal tubules

1995 ◽  
Vol 269 (1) ◽  
pp. F86-F92 ◽  
Author(s):  
G. T. Nagami
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Ammonia Production ◽  
Angiotensin Ii Receptor ◽  
Production Rates ◽  
Ammonia Metabolism ◽  
Luminal Perfusion ◽  
Total Ammonia ◽  
Secretion Rates ◽  
Stimulation Of

Angiotensin II is an important regulator of acid-base and ammonia metabolism in the proximal tubule. Because angiotensin II receptors exist on the apical membrane and because luminal fluid angiotensin II concentrations may be substantial, the effects of luminal angiotensin II on ammonia production rates and net luminal total ammonia (tNH3) secretion rates were examined in dissected mouse S2 proximal tubule segments. Ammonia production rates reflected the total release of ammonia via the basolateral and luminal aspects of the tubule, whereas net luminal secretion rates reflected the rates at which ammonia left the tubule via the luminal fluid leaving the distal end of the perfused segment. The results demonstrated that 1) luminal angiotensin II affected tNH3 production in a concentration-dependent fashion, 2) luminal angiotensin II at concentrations that stimulated tNH3 production could counteract the effect of inhibitory basolateral concentrations of angiotensin II, 3) the stimulation of tNH3 production and the rise in intracellular calcium concentration induced by 10(-10) M luminal angiotensin II were blocked by the addition of an angiotensin II receptor inhibitor, saralasin, or the calcium channel blocker nifedipine to the luminal perfusion solution, and 4) in contrast to basolateral angiotensin II, which inhibited net luminal tNH3 secretion, luminal angiotensin II stimulated amiloride-sensitive net luminal tNH3 secretion in parallel with stimulation of luminal fluid acidification. Thus luminal angiotensin II at physiological and superphysiological concentrations has important effects on ammonia production and transport in the proximal tubule that in some ways differ from the effects of basolateral angiotensin II.

scholarly journals Proximal tubule NHE3 activity is inhibited by beta-arrestin-biased angiotensin II type 1 receptor signaling

2015 ◽  
Vol 309 (8) ◽  
pp. C541-C550 ◽  
Author(s):  
Carla P. Carneiro de Morais ◽  
Juliano Z. Polidoro ◽  
Donna L. Ralph ◽  
Thaissa D. Pessoa ◽  
Maria Oliveira-Souza ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
G Protein ◽  
Extracellular Fluid ◽  
The Body ◽  
Type I ◽  
Ang Ii ◽  
Receptor Signaling

Physiological concentrations of angiotensin II (ANG II) upregulate the activity of Na+/H+ exchanger isoform 3 (NHE3) in the renal proximal tubule through activation of the ANG II type I (AT1) receptor/G protein-coupled signaling. This effect is key for maintenance of extracellular fluid volume homeostasis and blood pressure. Recent findings have shown that selective activation of the beta-arrestin-biased AT1 receptor signaling pathway induces diuresis and natriuresis independent of G protein-mediated signaling. This study tested the hypothesis that activation of this AT1 receptor/beta-arrestin signaling inhibits NHE3 activity in proximal tubule. To this end, we determined the effects of the compound TRV120023, which binds to the AT1R, blocks G-protein coupling, and stimulates beta-arrestin signaling on NHE3 function in vivo and in vitro. NHE3 activity was measured in both native proximal tubules, by stationary microperfusion, and in opossum proximal tubule (OKP) cells, by Na+-dependent intracellular pH recovery. We found that 10−7 M TRV120023 remarkably inhibited proximal tubule NHE3 activity both in vivo and in vitro. Additionally, stimulation of NHE3 by ANG II was completely suppressed by TRV120023 both in vivo as well as in vitro. Inhibition of NHE3 activity by TRV120023 was associated with a decrease in NHE3 surface expression in OKP cells and with a redistribution from the body to the base of the microvilli in the rat proximal tubule. These findings indicate that biased signaling of the beta-arrestin pathway through the AT1 receptor inhibits NHE3 activity in the proximal tubule at least in part due to changes in NHE3 subcellular localization.

scholarly journals Ammonia production and secretion by S3 proximal tubule segments from acidotic mice: role of ANG II

2004 ◽  
Vol 287 (4) ◽  
pp. F707-F712 ◽  
Author(s):  
Glenn T. Nagami
Keyword(s):  
Proximal Tubule ◽  
Ang Ii ◽  
Ammonia Production ◽  
Low Sodium ◽  
Luminal Perfusion ◽  
And Control ◽  
Acid Loading ◽  
Proximal Tubule Segments ◽  
Secretion Rates

ANG II has potent effects on ammonia production and secretion rates by the proximal tubule and is found in substantial concentrations in the lumen of the proximal tubule in vivo. Because our previous studies demonstrated that acid loading enhanced the stimulatory effects of ANG II on ammonia production and secretion by S2 proximal tubule segments, we examined the effect of ANG II on ammonia production and secretion by isolated, perfused S3 segments from nonacidotic control mice and acidotic mice given NH4Cl for 7 days. In the absence of ANG II, ammonia production and secretion rates were no different in S3 segments from acidotic and control mice. By contrast, when ANG II was present in the luminal perfusion solution, ammonia production and secretion rates were stimulated, in a losartan-inhibitable manner, to a greater extent in S3 segments from acidotic mice. Ammonia secretion rates in S3 segments were largely inhibited by perfusion with a low-sodium solution containing amiloride in the presence or absence of ANG II. These results demonstrated that isolated, perfused mouse S3 proximal tubule segments produce and secrete ammonia, that NH4Cl-induced acidosis does not affect the basal rates of ammonia production and secretion, and that ANG II, added to the luminal fluid, stimulates ammonia production and secretion to a greater extent in S3 segments from acidotic mice. These findings suggest that S3 segments, in the presence of ANG II, can contribute to the enhanced renal excretion that occurs with acid loading.

Gluconeogenesis from glutamine and lactate in the isolated humanrenal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline

2001 ◽  
Vol 360 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Agnès CONJARD ◽  
Mireille MARTIN ◽  
Jérôme GUITTON ◽  
Gabriel BAVEREL ◽  
Bernard FERRIER
Keyword(s):  
Proximal Tubule ◽  
Human Kidney ◽  
Glucose Production ◽  
Proximal Tubules ◽  
Renal Gluconeogenesis ◽  
Adrenaline Infusion ◽  
Gluconeogenic Substrates ◽  
Stimulation Of

Recent studies in vivo have suggested that, in humans in the postabsorptive state, the kidneys contribute a significant fraction of systemic gluconeogenesis, and that the stimulation of renal gluconeogenesis may fully explain the increase in systemic gluconeogenesis during adrenaline infusion. Given the potential importance of human renal gluconeogenesis in various physiological and pathophysiological situations, we have conducted a study in vitro to further characterize this metabolic process and its regulation. For this, successive segments (S1, S2 and S3) of human proximal tubules were dissected and incubated with physiological concentrations of glutamine or lactate, two potential gluconeogenic substrates that are taken up by the human kidney in vivo, and glucose production was measured. The effects of adrenaline, noradrenaline and cAMP, a well established stimulator of gluconeogenesis in animal kidney tubules, were also studied in suspensions of human renal proximal tubules. The results indicate that the three successive segments have about the same capacity to synthesize glucose from glutamine; by contrast, the S2 and S3 segments synthesize more glucose from lactate than the S1 segment. In the S2 and S3 segments, lactate appears to be a better gluconeogenic precursor than glutamine. The addition of cAMP, but not of adrenaline or noradrenaline, led to the stimulation of gluconeogenesis from lactate and glutamine by human proximal tubules. These results indicate that, in the human kidney in vivo, lactate might be the main gluconeogenic precursor, and that the stimulation of renal gluconeogenesis observed in vivo upon adrenaline infusion may result from an indirect action on the renal proximal tubule.

Effects of angiotensin II on the CO2 dependence of HCO3− reabsorption by the rabbit S2 renal proximal tubule

2006 ◽  
Vol 290 (3) ◽  
pp. F666-F673 ◽  
Author(s):  
Yuehan Zhou ◽  
Patrice Bouyer ◽  
Walter F. Boron
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Renal Proximal Tubule ◽  
Signal Transduction Pathways ◽  
Low Doses ◽  
Ang Ii ◽  
Reabsorption Rate ◽  
Fractional Inhibition

Previous authors showed that, at low doses, both basolateral and luminal ANG II increase the proximal tubule's HCO3− reabsorption rate ( JHCO3). Using out-of-equilibrium CO2/HCO3− solutions, we demonstrated that basolateral CO2 increases JHCO3. Here, we examine interactions between ANG II and CO2 in isolated, perfused rabbit S2 segments. We first used equilibrated 5% CO2/22 mM HCO3−/pH 7.40 in bath and lumen. At 10−11 M, basolateral (BL) ANG II increased JHCO3 by 41%, and luminal ANG II increased JHCO3 by 35%. At 10−9 M, basolateral ANG II decreased JHCO3 by 43%, whereas luminal ANG II was without effect. Second, we varied [CO2]BL from 0 to 20% at fixed [HCO3−]BL and pHBL. Fractional stimulation produced by BL 10−11 M ANG II falls when [CO2]BL exceeds 5%. Fractional inhibition produced by BL 10−9 M ANG II tends to rise when [CO2]BL exceeds 5%. Regarding luminal ANG II, fractional stimulation produced by 10−11 M ANG II fell monotonically as [CO2]BL rose from 0 to 20%. Fractional inhibition produced by 10−9 M ANG II rose monotonically with increasing [CO2]BL. Viewed differently, ANG II at 10−11 M tended to reduce stimulation by CO2, and at 10−9 M, produced an even greater reduction. In conclusion, the mutual effects of 1) ANG II on the JHCO3 response to basolateral CO2 and 2) basolateral CO2 on the JHCO3 responses to ANG II suggest that the signal-transduction pathways for ANG II and basolateral CO2 intersect or merge.

scholarly journals Angiotensin II counteracts the effects of cAMP/PKA on NHE3 activity and phosphorylation in proximal tubule cells

2016 ◽  
Vol 311 (5) ◽  
pp. C768-C776 ◽  
Author(s):  
Renato O. Crajoinas ◽  
Juliano Z. Polidoro ◽  
Carla P. A. Carneiro de Morais ◽  
Regiane C. Castelo-Branco ◽  
Adriana C. C. Girardi
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Intracellular Camp ◽  
Camp Accumulation ◽  
Ang Ii ◽  
Proximal Tubule Cells ◽  
Opossum Kidney ◽  
Subsequent Decrease

Binding of angiotensin II (ANG II) to the AT1 receptor (AT1R) in the proximal tubule stimulates Na+/H+ exchanger isoform 3 (NHE3) activity through multiple signaling pathways. However, the effects of ANG II/AT1R-induced inihibitory G protein (Gi) activation and subsequent decrease in cAMP accumulation on NHE3 regulation are not well established. We therefore tested the hypothesis that ANG II reduces cAMP/PKA-mediated phosphorylation of NHE3 on serine 552 and, in doing so, stimulates NHE3 activity. Under basal conditions, ANG II stimulated NHE3 activity but did not affect PKA-mediated NHE3 phosphorylation at serine 552 in opossum kidney (OKP) cells. However, in the presence of the cAMP-elevating agent forskolin (FSK), ANG II blocked FSK-induced NHE3 inhibition, reduced intracellular cAMP concentrations, lowered PKA activity, and prevented the FSK-mediated increase in NHE3 serine 552 phosphorylation. All effects of ANG II were blocked by pretreating OKP cells with the AT1R antagonist losartan, highlighting the contribution of the AT1R/Gi pathway in ANG II-mediated NHE3 upregulation under cAMP-elevating conditions. Accordingly, Gi inhibition by pertussis toxin treatment decreased NHE3 activity both in vitro and in vivo and, more importantly, prevented the stimulatory effect of ANG II on NHE3 activity in rat proximal tubules. Collectively, our results suggest that ANG II counteracts the effects of cAMP/PKA on NHE3 phosphorylation and inhibition by activating the AT1R/Gi pathway. Moreover, these findings support the notion that NHE3 dephosphorylation at serine 552 may represent a key event in the regulation of renal proximal tubule sodium handling by ANG II in the presence of natriuretic hormones that promote cAMP accumulation and transporter phosphorylation.

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