pH regulation in single glomerular mesangial cells. II. Na+-dependent and -independent Cl(-)-HCO3- exchangers

Boyarsky, G.; Ganz, Michael B.; Sterzel, R. Bernd; Boron, Walter F.

doi:10.1152/ajpcell.1988.255.6.c857

Cited by 152 publications

(93 citation statements)

References 8 publications

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“…The intrinsic buffering power (/i) was determined at different pHi as described (7,18,24,(26)(27)(28)(29)(30), by exposing the cells to 25 mM NH4Cl in Hepes, Na'-free buffered solutions and then decreasing the NH4C1 concentration by 5 or 10 mM for each step to 0 mM (n = 10). The Pi was then calculated from the midpoint change in pHi at each step.…”

Section: Methodsmentioning

confidence: 99%

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

Alvaro¹,

Guardia²,

Bini³

et al. 1995

J. Clin. Invest.

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To elucidate mechanisms of glucagon-induced bicarbonaterich choleresis, we investigated the effect of glucagon on ion transport processes involved in the regulation of intracellular pH (pH1) in isolated rat hepatocyte couplets. It was found that glucagon (200 nM), without influencing resting pH1, significantly stimulates the Cl-/HCO3 exchange activity.The effect of glucagon was associated with a sevenfold increase in cAMP levels in rat hepatocytes. The activity of the Cl-/HCO3-exchanger was also stimulated by DBcAMP + forskolin. The effect of glucagon on the Cl-/HCO3 exchange was individually blocked by two specific and selective inhibitors of protein kinase A, uM) and H-89 (30 ,uM), the latter having no influence on the glucagon-induced cAMP accumulation in isolated rat hepatocytes. The Cl -channel blocker, NPPB (10 pmM), showed no effect on either the basal or the glucagon-stimulated Cl-/ HCO3 exchange. In contrast, the protein kinase C agonist, PMA (10 jpM), completely blocked the glucagon stimulation of the C1-/HCO3 exchange; however, this effect was achieved through a significant inhibition of the glucagonstimulated cAMP accumulation in rat hepatocytes. Colchicine pretreatment inhibited the basal as well as the glucagon-stimulated Cl-/HCO3 exchange activity. The Na+/H+ exchanger was unaffected by glucagon either at basal pH1 or at acid pH, values. In contrast, glucagon, at basal pH1, stimulated the Na+-HCO-symport. The main findings of this study indicate that glucagon, through the cAMP-dependent protein kinase A pathway, stimulates the activity of the Cl-/HCO3 exchanger in isolated rat hepatocyte couplets, a mechanism which could account for the in vivo induced bicarbonate-rich choleresis. (J. Clin. Invest. 1995.

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Section: Methodsmentioning

confidence: 99%

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

Alvaro¹,

Guardia²,

Bini³

et al. 1995

J. Clin. Invest.

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“…Emission was detected at 525 nm after excitation at 445 and 495 nm. The 445:495 nm ratio was calculated after background subtraction, and calibration to pH i was performed using the 7-point nigericin/high-K + technique, essentially as described by Boyarsky et al (Boyarsky et al, 1988). The high-K + Ringer's solution was similar to the standard Ringer's solution, except that HCO 3 2 was omitted and the Ringer's contained 140 mM KCl and 10 mM NaCl.…”

Section: Measurements Of Ph Imentioning

confidence: 99%

PDGFRα signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways

Clement

Mally

Stock

et al. 2012

Journal of Cell Science

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SummaryIn fibroblasts, platelet-derived growth factor receptor alpha (PDGFRa) is upregulated during growth arrest and compartmentalized to the primary cilium. PDGF-AA mediated activation of the dimerized ciliary receptor produces a phosphorylation cascade through the PI3K-AKT and MEK1/2-ERK1/2 pathways leading to the activation of the Na + /H + exchanger, NHE1, cytoplasmic alkalinization and actin nucleation at the lamellipodium that supports directional cell migration. We here show that AKT and MEK1/2-ERK1/2-p90 RSK inhibition reduced PDGF-AA-induced cell migration by distinct mechanisms: AKT inhibition reduced NHE1 activity by blocking the translocation of NHE1 to the cell membrane. MEK1/2 inhibition did not affect NHE1 activity but influenced NHE1 localization, causing NHE1 to localize discontinuously in patches along the plasma membrane, rather than preferentially at the lamellipodium. We also provide direct evidence of NHE1 translocation through the cytoplasm to the leading edge. In conclusion, signals initiated at the primary cilium through the PDGFRaa cascade reorganize the cytoskeleton to regulate cell migration differentially through the AKT and the MEK1/2-ERK1/2-p90 RSK pathways. The AKT pathway is necessary for initiation of NHE1 translocation, presumably in vesicles, to the leading edge and for its activation. In contrast, the MEK1/2-ERK1/2-p90 RSK pathway controls the spatial organization of NHE1 translocation and incorporation, and therefore specifies the direction of the leading edge formation.

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“…However, a fall in pH i ought to inhibit NBCe1-A (Fig. 3), either directly or indirectly by lowering [HCO 3 Ϫ ] i and [CO 3 2Ϫ ] i , just as a fall in pH i inhibits Cl-HCO 3 exchange in other cell types (37)(38)(39)(40).…”

Section: Do Proximal Tubules Sense Acute Phi Changes?mentioning

confidence: 99%

Evidence from renal proximal tubules that \documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation}{\mathrm{HCO}}_{3}^{-}\end{equation}\end{document} and solute reabsorption are acutely regulated not by pH but by basolateral \documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackag

Zhou

Zhao

Bouyer

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Respiratory acidosis, a decrease in blood pH caused by a rise in [CO 2], rapidly triggers a compensatory response in which the kidney markedly increases its secretion of H ؉ from blood to urine. However, in this and other acid-base disturbances, the equilibrium CO 2 kidney ͉ out-of-equilibrium solution ͉ acid-base disturbances ͉ volume reabsorption A major task of the kidney is to secrete H ϩ into the urine.Inadequate renal H ϩ secretion caused, for example, by mutations to acid-base transporters (1-4) or carbonic anhydrases (5), or by renal failure (6, 7), can lead to a life-threatening decrease in blood pH. Moreover, to maintain a stable blood pH, the kidney must appropriately increase H ϩ secretion in response to metabolic acidosis (a decrease in blood pH caused by a decrease in [HCO 3 Ϫ ] at a fixed CO 2 ) or to respiratory acidosis. However, a half century after the classical observation that respiratory acidosis rapidly stimulates renal H ϩ secretion (8, 9), we still have little insight into how the kidney senses acute acid-base disturbances.The renal proximal tubule (PT) reabsorbs (from lumen to blood) a liquid that contains Ϸ80% of the HCO 3 Ϫ filtered by the glomerulus. The PT cell does this reabsorbtion by secreting H ϩ into the PT lumen and using this H ϩ to titrate luminal HCO 3 Ϫ to CO 2 and H 2 O. After entering the cell across the apical membrane, the CO 2 and H 2 O recombine to produce H ϩ and HCO 3 Ϫ . The cell extrudes the H ϩ into the lumen across the apical membrane through Na-H exchangers (10-12) and H ϩ pumps (13) and moves the HCO 3 Ϫ out across the basolateral membrane via the electrogenic Na͞HCO 3 cotransporter NBCe1-A (14, 15). Carbonic anhydrases catalyze the interconversions between CO 2 and H 2 O on the one hand and HCO 3 Ϫ and H ϩ on the other (5). Because blood pH is the parameter regulated by these acid-base transport processes, blood pH or, more likely, intracellular pH (pH i ), has been thought to be the parameter sensed by renal cells. However, because of the interconversion CO 2 ϩ H 2 O^HCO 3 In the present study, we perfused single, isolated S2 segments of rabbit PTs and collected the fluid that had passed along the PT lumen. Analysis of this collected fluid allowed us to compute volume reabsorption (J V ); HCO 3 Ϫ reabsorption (J HCO 3 ), which is virtually the same as the H ϩ -secretion rate under the conditions of our experiments; and the reabsorption of solutes other than NaHCO 3 (J Other ). We made the surprising observation that, at least in the short term, J HCO 3 and J Other do not respond to changes in basolateral or intracellular pH. The most straightforward hypothesis is that PT cells have sensors for basolateral HCO 3 Ϫ and a parameter related to CO 2 . Materials and MethodsExcept for the compositions of most of the OOE CO 2 ͞HCO 3 Ϫ solutions, our methods are described in detail in ref. 17.Tubule Perfusion. We hand dissected kidneys from ''pathogenfree'' female New Zealand White rabbits (1.4-2.0 kg) to yield individual segments of midcortical S2 PTs in accorda...

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pH regulation in single glomerular mesangial cells. II. Na+-dependent and -independent Cl(-)-HCO3- exchangers

Cited by 152 publications

References 8 publications

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

PDGFRα signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways

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