Effect of acute acidemia on phosphate uptake by renal proximal tubular brush-border membranes

1986 ◽  
Vol 251 (5) ◽  
pp. F889-F896
Author(s):  
B. S. Levine ◽  
J. A. Kraut ◽  
D. R. Mishler ◽  
P. W. Crooks
Keyword(s):  
Metabolic Acidosis ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Respiratory Acidosis ◽  
Tissue Slices ◽  
Pi Transport ◽  
Proximal Tubular ◽  
Renal Proximal Tubular ◽  
Plasma Phosphorus

Prolonged metabolic acidosis is associated with depressed phosphate (Pi) uptake by the brush-border membrane (BBM) of the proximal tubule. To examine if changes in systemic pH underlie this inhibition, we measured Pi transport by renal cortical BBM from thyroparathyroidectomized rats with respiratory or metabolic acidosis of 1 or 3 h, respectively, and in appropriate controls. Also, Pi transport was measured in BBM prepared using tissue slices from nonacidotic rats that were preincubated for 20 or 45 min at either pH 6.9 (HCO3 = 10 mM, CO2 = 10%) or 7.4 (HCO3 = 10 mM, CO2 = 2.5%). Despite comparable acidemia (pH 7.06 +/- 0.05 with respiratory acidosis and 7.10 +/- 0.03 with metabolic acidosis), Na-dependent Pi uptake at 5 s incubation was reduced by 15.2 +/- 3.5% with respiratory acidosis compared with paired controls. It was not altered with metabolic acidosis. Vmax in respiratory acidosis (1.2 nmol X mg protein-1 X 5 s-1) was less than in controls (1.6); Kt was similar in both groups. 22Na transport and Na-dependent glucose transport were unchanged. Plasma phosphorus (P) increased from 8.75 +/- 0.35 mg/dl to 12.42 +/- 1.9 with respiratory acidosis. Therefore BBM vesicles transport was measured in controls after plasma P was raised. Under these conditions, Pi transport was similar to that with respiratory acidosis. Also Pi transport by BBM was unchanged when tissue slices were preincubated in vitro at high CO2 concentrations for 20 or 45 min. Thus respiratory acidosis specifically inhibits Na-dependent Pi transport by decreasing the number or rate of the BBM Pi carrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of maleic acid-induced glucosuria in dog kidney

1976 ◽  
Vol 231 (4) ◽  
pp. 1024-1032 ◽  
Author(s):  
M Silverman ◽  
L Huang
Keyword(s):  
Brush Border ◽  
Maleic Acid ◽  
Brush Border Membrane ◽  
Multiple Indicator Dilution ◽  
Dog Kidney ◽  
Proximal Tubular ◽  
Multiple Indicator ◽  
Prior Administration

The multiple indicator-dilution technique in vivo and isolated brush-border membranes in vitro have been used to explore the mechanism of maleic acid-induced glucosuria in dog kidney. The interaction of D-glucose with the antiluminal membrane from the peritubular fluid surface is unaltered. It is demonstrated that alpha-methyl-D-glucoside (alpha MG) enters and exits from the proximal tubular cell only across the brush-border membrane. Then using alphaMG as a reference indicator, it is shown that maleic acid does not cause complete inhibition of D-glucose interaction with the antiluminal membrane from the cytoplasmic surface. The binding of [3H]phlorizin both in vivo and in vitro is not affected by prior administration of maleic acid, indicating that D-glucose interaction with the outside surface of the brush border is also not affected by maleic acid. The data are therefore consistent with the concept that maleic acid-induced glucosuria is due either to i) partial inhibition of D-glucose movement from cytoplasm across the antiluminal membrane into the blood, ii) stimulated movement back across the brush-border membrane into urine, or iii) a combination of the two effects.

Insulin stimulates Pi transport in brush border vesicles from proximal tubular segments

1984 ◽  
Vol 247 (5) ◽  
pp. E616-E624 ◽  
Author(s):  
M. R. Hammerman ◽  
S. Rogers ◽  
V. A. Hansen ◽  
J. R. Gavin
Keyword(s):  
Proximal Tubule ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Direct Action ◽  
Membrane Vesicles ◽  
Pi Transport ◽  
Glomerular Filtrate ◽  
Dog Kidney ◽  
Proximal Tubular ◽  
Altered Transport

Induction of hyperinsulinemia in dogs results in enhanced reabsorption of Pi from glomerular filtrate in the renal proximal tubule. To determine whether this may be a direct action of insulin mediated by altered transport characteristics of the proximal tubular brush border membrane, we measured Na+-dependent 32Pi transport in brush border membrane vesicles prepared from isolated proximal tubular segments originating from dog kidney that had been incubated with or without insulin. Specific high affinity binding sites for insulin were detected in proximal tubular segments. Increased initial rates (15 s) of Na+-dependent 32Pi transport were measured in brush border vesicles prepared from segments that had been incubated with insulin. This effect of insulin was concentration dependent over the range of 10(-10) to 10(-6) M insulin. These studies demonstrate the feasibility of using brush border vesicles prepared from proximal tubular segments to study solute transport. Our findings suggest that insulin-induced increased Pi reabsorption in the proximal tubule is mediated by a direct action of insulin on the proximal tubular cell, which results in increased Na+-Pi cotransport across the brush border membrane.

Enhancement of Gentamicin-Induced Inhibition of Phosphatidylinositol Hydrolysis in Rabbit Renal Proximal Tubular Brush-Border Membrane by Furosemide

Renal Failure ◽  
1989 ◽  
Vol 11 (2-3) ◽  
pp. 105-109 ◽  
Author(s):  
Hajime Nakahama ◽  
SungHyo Shin ◽  
Toshiki Moriyama ◽  
Masahiro Kakihara ◽  
Yoshifumi Fukuhara ◽  
...  
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

Actions of NAD+ on renal brush border transport of phosphate in vivo and in vitro

1985 ◽  
Vol 249 (6) ◽  
pp. F948-F955 ◽  
Author(s):  
S. A. Kempson ◽  
S. T. Turner ◽  
A. N. Yusufi ◽  
T. P. Dousa
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Competitive Inhibition ◽  
Inhibitory Effect ◽  
Pi Transport ◽  
Renal Brush Border Membrane ◽  
Dependent Transport ◽  
Renal Brush Border

Previous studies showed that an increase in NAD+ content in renal cortex in vivo was accompanied by specific inhibition of Na+-dependent inorganic phosphate (Pi) transport across the renal brush border membrane (BBM). Further, in vitro addition of NAD+ to isolated renal BBM vesicles specifically inhibited Na+ gradient-dependent transport of Pi. The present study examined some aspects of the mechanism of this inhibition by NAD+ in vitro and in vivo. When NAD+ was increased in vivo by nicotinamide injection, the apparent Vmax was decreased, but the apparent Km was not different, indicating apparent noncompetitive inhibition. In the presence of 0.3 mM NAD+ added in vitro, the apparent Km for Na+-dependent Pi transport by BBM vesicles was increased, whereas the apparent Vmax was unchanged, indicating apparent competitive inhibition. These changes in apparent Km and apparent Vmax were identical when Pi uptake was measured either at 30-s or at 5-s (the initial rate) incubation times. Inhibition of Pi transport by BBM vesicles in vitro was due primarily to the action of intact added NAD+, although there may be some contribution by isotope dilution due to Pi released from NAD+ by enzymatic hydrolysis. Although in vitro inhibition of Pi transport by added NAD+ was reversed by washing the BBM, the inhibition due to increased NAD+ in vivo persisted after extensive washing of the isolated BBM. The specificity of the inhibitory effect of NAD+ in vivo was indicated by the finding that changes in renal cortical content of ATP or Pi, evoked by loading with glycerol or fructose, did not change BBM transport of Pi.(ABSTRACT TRUNCATED AT 250 WORDS)

Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms

2000 ◽  
Vol 80 (4) ◽  
pp. 1373-1409 ◽  
Author(s):  
Heini Murer ◽  
Nati Hernando ◽  
Ian Forster ◽  
Jürg Biber
Keyword(s):  
Brush Border ◽  
Molecular Mechanisms ◽  
Brush Border Membrane ◽  
Cell Model ◽  
Expression System ◽  
Cellular Mechanisms ◽  
Membrane Expression ◽  
Renal Brush Border Membrane ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

Renal proximal tubular reabsorption of Pi is a key element in overall Pi homeostasis, and it involves a secondary active Pi transport mechanism. Among the molecularly identified sodium-phosphate (Na/Pi) cotransport systems a brush-border membrane type IIa Na-Pi cotransporter is the key player in proximal tubular Pi reabsorption. Physiological and pathophysiological alterations in renal Pi reabsorption are related to altered brush-border membrane expression/content of the type IIa Na-Picotransporter. Complex membrane retrieval/insertion mechanisms are involved in modulating transporter content in the brush-border membrane. In a tissue culture model (OK cells) expressing intrinsically the type IIa Na-Pi cotransporter, the cellular cascades involved in “physiological/pathophysiological” control of Pi reabsorption have been explored. As this cell model offers a “proximal tubular” environment, it is useful for characterization (in heterologous expression studies) of the cellular/molecular requirements for transport regulation. Finally, the oocyte expression system has permitted a thorough characterization of the transport characteristics and of structure/function relationships. Thus the cloning of the type IIa Na-Pi cotransporter (in 1993) provided the tools to study renal brush-border membrane Na-Pi cotransport function/regulation at the cellular/molecular level as well as at the organ level and led to an understanding of cellular mechanisms involved in control of proximal tubular Pi handling and, thus, of overall Pihomeostasis.

Glucocorticoids and metabolic acidosis-induced renal transports of inorganic phosphate, calcium, and NH4

1986 ◽  
Vol 250 (5) ◽  
pp. F827-F833 ◽  
Author(s):  
M. Boross ◽  
J. Kinsella ◽  
L. Cheng ◽  
B. Sacktor
Keyword(s):  
Metabolic Acidosis ◽  
Brush Border ◽  
Inorganic Phosphate ◽  
Brush Border Membrane ◽  
Adrenal Glands ◽  
Initial Rate ◽  
Membrane Vesicles ◽  
Ammonium Excretion ◽  
Pi Transport ◽  
Rat Proximal Tubule

The initial rate (5 s) of Na+-dependent inorganic phosphate (Pi) uptake in brush-border membrane vesicles isolated from rat proximal tubule was decreased in metabolic acidosis, 0.42 +/- 0.02 vs. 0.59 +/- 0.05 nmol/mg protein, in vesicles from control animals. Phosphate, ammonium, and Ca2+ excretions were increased 100, 600, and 56%, respectively. These changes in brush-border Pi transport and urinary excretion of ions were largely dependent on intact adrenal glands. After adrenalectomy there were no significant changes in brush-border Pi transport, Pi, and Ca2+ excretion, whereas ammonium excretion increased only 300% compared with controls. When the glucocorticoid dexamethasone was administered to adrenalectomized animals, it mimicked the effects of metabolic acidosis both in the presence and the absence of metabolic acidosis. The initial rate of brush-border Pi transport was decreased by dexamethasone administration to 0.37 +/- 0.04 nmol/mg protein in adrenalectomized acidotic animals and 0.39 +/- 0.03 nmol/mg protein in adrenalectomized animals. Dexamethasone administered to adrenalectomized acidotic animals increased Pi, ammonium, and Ca2+ excretion 190, 690, and 23%, respectively. Dexamethasone administered to nonacidotic adrenalectomized animals increased Pi ammonium and Ca2+ excretion 165, 240, and 31%, respectively. We conclude that changes in Pi, ammonium, and Ca2+ excretion observed during metabolic acidosis were dependent on intact adrenal glands and that glucocorticoids administered to adrenalectomized acidotic or nonacidotic animals mimicked the changes observed in acidotic animals with intact adrenal glands.

scholarly journals Phosphate Transport in Pig Proximal Small Intestines during Postnatal Development: Lack of Modulation by Calcitriol*

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1500-1507 ◽  
Author(s):  
Bernd Schröder ◽  
Olaf Hattenhauer ◽  
Gerhard Breves
Keyword(s):  
Postnatal Development ◽  
Vitamin D3 ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Ussing Chamber ◽  
Maximum Velocity ◽  
Phosphate Transport ◽  
Pi Transport ◽  
Small Intestines

Abstract The role of calcitriol in the intestinal absorption of inorganic phosphate (Pi) during postnatal development was studied in newborn [<1 week postpartum (pp)], suckling (3–4 weeks pp), and weaned (>6 weeks pp) control piglets (con) and piglets suffering from inherited calcitriol deficiency (def). In addition, a number of def piglets were treated with vitamin D3 (def-D3). Regardless of age, plasma calcitriol concentrations in def piglets were unphysiologically low (16–21 pg/ml) and differed significantly from those in respective con animals (60–69 pg/ml) and vitamin D3-treated def piglets (50–56 pg/ml). However, newborn and suckling def piglets had normal Ca (∼3.0 mmol/liter) and Pi (∼2.8 mmol/liter) plasma levels. Def piglets became hypocalcemic (1.9 mmol/liter) and hypophosphatemic (1.9 mmol/liter) between 4–6 weeks pp. Treatment with vitamin D3 significantly increased plasma Ca (3.2 mmol/liter) and Pi (2.7 mmol/liter) levels in weaned def animals. Regardless of calcitriol status, net Pi flux rates (active Pi absorption, as determined with the in vitro Ussing-chamber technique) from the upper small intestines was maximal at birth [170–224 nmol/(cm2·h)] and decreased by approximately 80% during the first week of life before remaining constant [30–50 nmol/(cm2·h)] during the following development. In weaned def piglets, net Pi flux rates were significantly lower by about 80% compared with those in con animals. Treatment of def piglets with vitamin D3 had no effect in newborn and suckling animals but reconstituted net Pi flux rates to normal values at weaning age. Age-dependent and calcitriol-mediated changes in net Pi flux rates were paralleled by respective maximum velocity values of Na+-dependent Pi uptake across the brush border membrane of the enterocytes (newborn piglets, 1.9–2.2 nmol/(mg protein·10 sec); suckling piglets, 0.4–0.6 nmol/(mg protein·10 sec); weaned piglets, 0.7, 0.3, and 0.7 nmol/(mg protein·10 sec) in con, def, and def-D3 animals, respectively). These findings suggest that the apical Pi uptake represents the major rate-limiting step of the overall transepithelial Pi transport. At weaning, Na+/Pi transport across the intestinal brush-border membrane is clearly stimulated by calcitriol, but no significant effects of age or calcitriol on the Km values (0.5–0.7 mmol/liter) were observed. In conclusion, our findings reveal calcitriol-independent mechanisms for active intestinal Pi absorption during the neonatal and suckling periods. The onset of the classical calcitriol-dependent mechanism for active intestinal Pi absorption does not occur until weaning.

Characterization and distribution of albumin binding protein in normal rat kidney

1996 ◽  
Vol 271 (1) ◽  
pp. F101-F107 ◽  
Author(s):  
A. L. Cessac-Guillemet ◽  
F. Mounier ◽  
C. Borot ◽  
H. Bakala ◽  
M. Perichon ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Binding Protein ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Albumin Binding ◽  
Renal Brush Border Membrane ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

The mechanism by which proteins that pass through the glomerular basal lamina are taken up by proximal tubule cells is incompletely characterized. Past work has identified the kinetics of albumin binding to renal brush-border membrane. We have now purified and characterized albumin binding protein (ABP) and shown its distribution in renal proximal tubular cells. ABP was purified from rat renal proximal tubular cell brush-border membrane by affinity chromatography with rat serum albumin-Sepharose. The resulting ABP had two apparent molecular masses (55 and 31 kDa) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antibodies to ABP were raised in rabbits and checked by immunoassay and immunoblotting. Light-microscopic immunohistochemistry showed ABP all along the proximal tubule in the pars convoluta and pars recta. Electron-microscopic immunohistochemistry showed labeling on microvilli and in apical endocytic vacuoles, dense apical tubules, and lysosomes. These results indicate that ABP is involved in proximal tubule endocytosis.

Metabolic acidosis and parathyroidectomy increase Na+-H+ exchange in brush border vesicles

1983 ◽  
Vol 245 (2) ◽  
pp. F217-F222 ◽  
Author(s):  
D. E. Cohn ◽  
S. Klahr ◽  
M. R. Hammerman
Keyword(s):  
Metabolic Acidosis ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Brush Border Membrane Vesicles ◽  
Chronic Metabolic Acidosis ◽  
Renal Brush Border Membrane ◽  
Dog Kidney ◽  
Renal Proximal Tubular ◽  
Renal Brush Border

Na+-H+ exchange across the brush border membrane of the renal proximal tubular cell is a mechanism for Na+ reabsorption and H+ secretion. An electroneutral Na+-H+ exchange activity has been identified in isolated renal brush border membrane vesicles from rat and dog kidney, and increased Na+-H+ exchange has been measured in brush border membrane vesicles from remnant kidneys of dogs with chronic renal failure. To ascertain whether changes in H+ secretion by the kidney observed in chronic metabolic acidosis and in states of altered parathyroid function might result from altered Na+-H+ exchange across the renal cortical cellular brush border membrane, we measured Na+-H+ exchange in brush border membrane vesicles from kidneys of dogs with chronic metabolic acidosis and from kidneys of thyroparathyroidectomized dogs. Increased amiloride-sensitive Na+-H+ exchange was demonstrated in brush border membrane vesicles from kidneys of both groups of dogs, suggesting that adaptations in H+ excretion in chronic metabolic acidosis and hypoparathyroidism might be explained by increased activity of a renal brush border membrane Na+-H+ exchanger.

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