Proximal tubular dopamine production regulates basolateral Na-K-ATPase

1992 ◽  
Vol 262 (4) ◽  
pp. F566-F571 ◽  
Author(s):  
A. D. Baines ◽  
P. Ho ◽  
R. Drangova
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Sch 23390 ◽  
Basolateral Membrane ◽  
Sodium Dodecyl ◽  
Maximal Activity ◽  
Western Blots ◽  
Salt Diet ◽  
Low Salt ◽  
Proximal Tubular

Regulation of proximal tubular Na-K-adenosine-triphosphatase (ATPase), brush-border membrane Na(+)-H+ antiporter and Na(+)-Pi symporter activity by endogenously produced dopamine was examined in Wistar rats. Na-K-ATPase was measured in basolateral membrane (BLM) fractions permeabilized with alamethicin or sodium dodecyl sulfate (SDS). Carbidopa (5 mg/kg) injected 18 h before removal of kidneys increased maximal activity (Vmax) noncompetitively in cortical BLM but not in other membrane fractions or outer medullary BLM (-2 +/- 4%). Chronic renal denervation did not alter the response. Carbidopa stimulated Na-K-ATPase in cortical BLM from rats eating a normal salt diet with and without 1% saline to drink (+18 +/- 4% and +22 +/- 4%, respectively; P greater than 0.001). Carbidopa did not increase Vmax of BLM Na-K-ATPase from rats eating a low-salt diet (+1.5 +/- 4%); however, when the low-salt diet was supplemented with 1 mM dihydroxyphenylalanine (dopa) to drink for 1 day carbidopa, increased Vmax by 18 +/- 3% (P = 0.018). Carbidopa did not alter the Michaelis constant (Km) for Na or K or inhibitory constant (Ki) for ouabain. Injection of the DA1 antagonist Sch 23390 (2 mg/kg) also increased Na-K-ATPase (18 +/- 4%; P = 0.014). Western blots using a monoclonal alpha-subunit antibody revealed a 22 +/- 8% increase following carbidopa treatment (P = 0.033; n = 19 pairs). Carbidopa had no effect on Na(+)-H+ antiporter activity (22Na uptake) or on Na(+)-32Pi cotransport in brush-border membrane vesicles. These results indicate that dopamine produced in proximal tubules tonically reduces Na-K-ATPase Vmax by decreasing the number of alpha-subunits associated with the BLM.

Endogenous renal dopamine production regulates phosphate excretion

1994 ◽  
Vol 266 (6) ◽  
pp. F858-F867 ◽  
Author(s):  
A. Debska-Slizien ◽  
P. Ho ◽  
R. Drangova ◽  
A. D. Baines
Keyword(s):  
Brush Border Membrane ◽  
Membrane Vesicle ◽  
Basolateral Membrane ◽  
High Salt Diet ◽  
Salt Diet ◽  
Endogenous Dopamine ◽  
Low Salt ◽  
32P Uptake ◽  
22Na Uptake ◽  
Renal Dopamine

We examined the effect of endogenous dopamine production on Pi and citrate excretion by Wistar rats. Carbidopa (20-40 mumol/kg ip) decreased dopamine, Pi, and citrate excretion within 20 min (86%, 47%, and 38%, respectively); Pi reabsorption increased 11 +/- 4% (P = 0.03). The decreases were sustained for at least 18 h. 3-Hydroxybenzylhydrazine (45 mumol/kg ip) reduced Pi excretion 24%. Benserazide (40 mumol/kg ip and 0.1 mumol/min iv) reduced dopamine excretion (94%) and blocked the effect of carbidopa on Pi and citrate excretion. In isolated perfused kidneys benserazide, carbidopa, and 3-hydroxybenzylhydrazine all decreased Pi excretion. Dopamine (1 mumol/l) added to cortical minceates reduced brush-border membrane vesicle (BBMV) 32P uptake by 8% (P < 0.02) and amiloride-inhibitable 22Na uptake by 19%. Carbidopa added to minceates increased 32P uptake by 12%. Carbidopa pretreatment increased (75%) amiloride-sensitive 22Na uptake into BBMV of rats fed a high-salt diet. Uptake was not increased into BBMV from rats fed a low-salt diet. Carbidopa increased (17%) basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) gradually over 4 h. Na(+)-K(+)-ATPase did not increase in rats fed a low-phosphorous diet, but did increase when dopa was added to the diet. Thus endogenous dopamine appears to directly control Na(+)-Pi and Na+/H+ transport and secondarily alter basolateral membrane Na(+)-K(+)-ATPase.

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.

Analysis of the Heymann nephritogenic glycoprotein in rat, mouse, and human kidney

1986 ◽  
Vol 64 (5) ◽  
pp. 441-447 ◽  
Author(s):  
P. R. Goodyer ◽  
M. Mills ◽  
B. S. Kaplan
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Sodium Dodecyl ◽  
Human Kidney ◽  
Western Blots ◽  
Reactive Material ◽  
Glomerular Epithelial Cell ◽  
Heymann Nephritis ◽  
Renal Brush Border Membrane ◽  
Epithelial Cell Surface

Passive Heymann nephritis is induced in rats by intravenous administration of antiserum raised against antigens of the renal proximal tubule. Evidence by Kerjaschki and Farquhar indicates that the critical nephritogenic is a high molecular weight glycoprotein (HMWgp) of rat renal brush border membrane. Their immunocytochemical studies also localize the nephritogenic antigen to the glomerular epithelial cell surface and may explain in situ formation of immune complexes at this locus in Heymann nephritis. We have confirmed the observations of Kerjaschki and Farquhar by demonstrating the HMWgp in extracts of rat brush border membrane and isolated glomeruli on sodium dodecyl sulphate – polyacrylamide (SDS–PA) (5%) gels. An antiserum raised to purified rat HMWgp identifies the antigen from rat or mouse kidney on Western blots. However, unlike rodent kidney, we were unable to detect a comparable HMWgp in extracts of human kidney on SDS–PA gels and found no cross-reactive material on Western blots of human brush border membrane proteins. Our observations suggest that human kidney lacks the nephritogenic antigen critical to initiation of Heymann nephritis in rodents.

Low-affinity transport of pyroglutamyl-histidine in renal brush-border membrane vesicles

1989 ◽  
Vol 257 (5) ◽  
pp. C971-C975 ◽  
Author(s):  
H. A. Skopicki ◽  
K. Fisher ◽  
D. Zikos ◽  
G. Flouret ◽  
D. R. Peterson
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Brush Border Membrane Vesicles ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Luminal Membrane ◽  
Renal Brush Border Membrane ◽  
Proximal Tubular ◽  
Renal Brush Border

These studies were performed to determine if a low-affinity carrier is present in the luminal membrane of proximal tubular cells for the transport of the dipeptide, pyroglutamyl-histidine (pGlu-His). We have previously described the existence of a specific, high-affinity, low-capacity [transport constant (Kt) = 9.3 X 10(-8) M, Vmax = 6.1 X 10(-12) mol.mg-1.min-1] carrier for pGlu-His in renal brush-border membrane vesicles. In the present study, we sought to demonstrate that multiple carriers exist for the transport of a single dipeptide by determining whether a low-affinity carrier also exists for the uptake of pGlu-His. Transport of pGlu-His into brush-border membrane vesicles was saturable over the concentration range of 10(-5)-10(-3) M, yielding a Kt of 6.3 X 10(-5) M and a Vmax of 2.2 X 10(-10) mol.mg-1.min-1. Uptake was inhibited by the dipeptides glycyl-proline, glycyl-sarcosine, and carnosine but not by the tripeptide pyroglutamyl-histidyl-prolinamide. We conclude that 1) pGlu-His is transported across the luminal membrane of the proximal tubule by multiple carriers and 2) the lower affinity carrier, unlike the higher affinity carrier, is nonspecific with respect to other dipeptides.

scholarly journals Renal effects of the serine protease inhibitor aprotinin in healthy conscious mice

2021 ◽  
Author(s):  
Stefan Wörner ◽  
Bernhard N. Bohnert ◽  
Matthias Wörn ◽  
Mengyun Xiao ◽  
Andrea Janessa ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Kidney Injury ◽  
Serine Protease Inhibitor ◽  
Tubular Function ◽  
Proteolytic Activation ◽  
Salt Diet ◽  
Low Salt ◽  
Proximal Tubular ◽  
Proximal Tubular Function

AbstractTreatment with aprotinin, a broad-spectrum serine protease inhibitor with a molecular weight of 6512 Da, was associated with acute kidney injury, which was one of the reasons for withdrawal from the market in 2007. Inhibition of renal serine proteases regulating the epithelial sodium channel ENaC could be a possible mechanism. Herein, we studied the effect of aprotinin in wild-type 129S1/SvImJ mice on sodium handling, tubular function, and integrity under a control and low-salt diet. Mice were studied in metabolic cages, and aprotinin was delivered by subcutaneously implanted sustained release pellets (2 mg/day over 10 days). Mean urinary aprotinin concentration ranged between 642 ± 135 (day 2) and 127 ± 16 (day 8) µg/mL . Aprotinin caused impaired sodium preservation under a low-salt diet while stimulating excessive hyperaldosteronism and unexpectedly, proteolytic activation of ENaC. Aprotinin inhibited proximal tubular function leading to glucosuria and proteinuria. Plasma urea and cystatin C concentration increased significantly under aprotinin treatment. Kidney tissues from aprotinin-treated mice showed accumulation of intracellular aprotinin and expression of the kidney injury molecule 1 (KIM-1). In electron microscopy, electron-dense deposits were observed. There was no evidence for kidney injury in mice treated with a lower aprotinin dose (0.5 mg/day). In conclusion, high doses of aprotinin exert nephrotoxic effects by accumulation in the tubular system of healthy mice, leading to inhibition of proximal tubular function and counterregulatory stimulation of ENaC-mediated sodium transport.

Effect of chronic inflammation on electrolyte transport in rabbit ileal villus and crypt cells

1997 ◽  
Vol 272 (4) ◽  
pp. G732-G741 ◽  
Author(s):  
U. Sundaram ◽  
A. B. West
Keyword(s):  
Chronic Inflammation ◽  
Inflammatory Mediators ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Basolateral Membrane ◽  
Rabbit Model ◽  
Electrolyte Transport ◽  
Acid Load ◽  
Crypt Cells ◽  
Stimulation Of

The effect of chronic inflammation on electrolyte transport in rabbit ileal villus and crypt cells was determined with the use of a rabbit model of chronic ileitis. In both cells, Na+/H+ exchange was monitored by following recovery from an acid load, and Cl-/HCO3- exchange was monitored by following recovery from an alkaline load. In villus cells, recovery from an acid load was not affected; however, recovery from an alkaline load was slowed. These data suggest that chronic inflammation inhibits Cl-/HCO3- exchange in villus cells. In contrast, in crypt cells, recovery from an alkaline load was unaffected, whereas recovery from an acid load was accelerated. These data suggest that chronic inflammation stimulates Na+/H+ exchange in crypt cells. Inhibition of Cl-/HCO3- exchange in villus cells would be expected to inhibit coupled NaCl absorption, which occurs by the coupling of brush-border membrane (BBM) Na+/H+ and Cl-/HCO3- exchange. Stimulation of Na+/H+ exchange in crypt cells, known to be present only on the basolateral membrane, alkalinizes the cell. This alkalinization may stimulate BBM Cl-/HCO3- exchange, resulting in HCO3- secretion. Thus these unique alterations in transporter activity suggest that different endogenous immune-inflammatory mediators may have differing effects on specific transporters in villus and crypt cells in the chronically inflamed ileum.

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.

Pi transport, phosphorylation, and dephosphorylation in renal membranes from HYP/Y mice

1983 ◽  
Vol 245 (6) ◽  
pp. F701-F706
Author(s):  
M. R. Hammerman ◽  
L. R. Chase
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Sodium Dodecyl ◽  
Membrane Vesicles ◽  
Hypophosphatemic Rickets ◽  
Dependent Protein Kinase ◽  
Phosphoprotein Phosphatase ◽  
Pi Transport ◽  
Dependent Protein ◽  
Renal Tubular

To ascertain whether cAMP-dependent phosphorylation could be demonstrated in brush border membrane vesicles (BBMV) isolated from kidneys of mice with X-linked hypophosphatemic rickets (HYP/Y) and normal littermates (+/Y) and, if so, to determine whether the absence of dephosphorylation might underlie differences in Na+-dependent 32Pi transport in BBMV, we measured 1) 32Pi transport, 2) cAMP-dependent phosphorylation, and 3) dephosphorylation in BBMV from +/Y and HYP/Y mice. Na+ gradient-dependent 32Pi transport was decreased in BBMV from HYP/Y mice as reflected in a decreased apparent Vmax. cAMP-dependent phosphorylation of a 62,000 Mr protein was demonstrated in sodium dodecyl sulfate polyacrylamide gels of BBMV from +/Y and HYP/Y mice and was associated with decreased Na+-dependent 32Pi transport. Dephosphorylation of the 62,000 Mr band was demonstrable in both types of membranes. Thus, both cAMP-dependent protein kinase and phosphoprotein phosphatase activities were demonstrable in BBMV isolated from +/Y and HYP/Y mice. These results are consistent with the renal tubular defect in the HYP/Y mouse reflecting an intrinsic abnormality of Pi transport in the brush border membrane independent from mediation of the phosphaturic effect of parathyroid hormone.

Developmental maturation of Na(+)-H+ exchange in rat renal tubular brush-border membrane

1991 ◽  
Vol 261 (6) ◽  
pp. F1017-F1025 ◽  
Author(s):  
I. Zelikovic ◽  
E. Stejskal ◽  
P. Lohstroh ◽  
A. Budreau ◽  
R. W. Chesney
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Initial Rate ◽  
Neonatal Rat ◽  
Adult Rats ◽  
Luminal Membrane ◽  
Age Related ◽  
Proximal Tubular ◽  
Na Uptake ◽  
Developmental Maturation

The developmental maturation of the Na(+)-H+ exchanger present in the proximal tubular luminal membrane of the rat was investigated. An overshoot of 1 mM Na+ uptake was evident in brush-border membrane vesicles derived from the renal cortex of 7- and 21-day-old and adult rats in the presence of an outwardly directed H+ concentration ([H+]) gradient [intravesicular pH (pHi) = 5.5; extravesicular pH (pHo) = 7.5]. Na+ uptake was amiloride sensitive at all ages examined. Significantly higher initial rate (3 s) Na+ uptake and peak accumulation (60 s) in the presence of a [H+] gradient were found in vesicles from 7-day-old rats compared with adult animals. Significantly enhanced initial rate Na+ uptake by neonatal vesicles was also evident under pH-equilibrated conditions (pHi = pHo = 7.5). An age-related decrease in amiloride-sensitive Na+ accumulation by vesicles was found. Kinetic analysis of Na(+)-H+ exchange in voltage-clamped vesicles, in the presence of dimethylamiloride (DMA), and calculating 5-s Na+ uptake values showed a maturational decrease in capacity (decreasing Vmax) coupled with a maturational increase in affinity (decreasing Km) of Na(+)-H+ antiport. These data suggest that an enhanced amiloride-inhibitable Na(+)-H+ exchange activity due to increased capacity of exchange exists in the proximal tubular luminal membrane of the neonatal rat. This increased Na(+)-H+ exchange may potentially contribute to positive Na+ balance in the growing organism and may rapidly dissipate the electrochemical Na+ gradient across the luminal membrane necessary for Na(+)-solute contransport, thereby contributing to glycosuria and aminoaciduria of early life.

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.

Sign in / Sign up

Export Citation Format

Share Document