Effect of luminal pH and HCO3- on phosphate reabsorption in the rabbit proximal convoluted tubule

1984 ◽  
Vol 247 (1) ◽  
pp. F25-F34
Author(s):  
L. L. Hamm ◽  
J. P. Kokko ◽  
H. R. Jacobson
Keyword(s):  
Proximal Tubule ◽  
Proximal Convoluted Tubule ◽  
Phosphate Reabsorption ◽  
Luminal Membrane ◽  
Glucose Flux ◽  
Glucose Reabsorption ◽  
All Solutions ◽  
Qualitative Effect ◽  
Phosphate Flux ◽  
Luminal Ph

Luminal pH in the proximal convoluted tubule may alter phosphate reabsorption in a variety of acid-base disturbances and in normal conditions as luminal pH decreases along the length of the proximal tubule. These studies address the influence of luminal pH on phosphate reabsorption in isolated perfused proximal convoluted tubules from normal rabbits. Initial perfusates were either pH 6.2 or 7.4, and the bath pH was 7.4. All solutions contained 10 mM total phosphate. The first experiments used HCO3-/CO2-free solutions to examine the effect of luminal pH independent of changes in [HCO3-] or Pco2. Lumen-to-bath phosphate flux increased from 0.63 +/- 0.23 with alkaline perfusate to 2.04 +/- 0.35 pmol X mm-1 X min-1 with acid perfusate. In a separate group of tubules, acetazolamide had no qualitative effect on this result. With HCO3-/CO2-containing solutions, phosphate reabsorption increased from 4.53 +/- 1.46 with alkaline perfusate to 9.67 +/- 1.77 pmol X mm-1 X min-1 with acid perfusate. Thus, an acid luminal fluid can enhance proximal phosphate reabsorption independent of the presence or absence of HCO3-/CO2. To examine the specificity of this effect, the influence of luminal pH on another solute (glucose), reabsorbed via a Na+-coupled mechanism, was studied. Lumen-to-bath glucose flux increased in the same direction: from 52.78 +/- 4.91 with alkaline perfusate to 57.13 +/- 4.70 pmol X mm-1 X min-1 with acid perfusate. The mechanism of the influence of luminal pH on phosphate and glucose reabsorption is not explained but could be direct or indirect from changes in intracellular pH, Na+ activity, metabolism, or basolateral transport. Since an acid luminal pH is expected to inhibit or decrease Na+-H+ exchange at the luminal membrane, these results are also consistent with a competition for the available Na+ gradient between phosphate and glucose transport and the Na+-H+ exchanger in the proximal tubule.

Proximal tubule site of inhibition of phosphate reabsorption by calcitonin

1984 ◽  
Vol 246 (6) ◽  
pp. F927-F930 ◽  
Author(s):  
T. J. Berndt ◽  
F. G. Knox
Keyword(s):  
Proximal Tubule ◽  
Salmon Calcitonin ◽  
Distal Tubule ◽  
Proximal Convoluted Tubule ◽  
Phosphate Reabsorption

The present study was performed to evaluate the nephron site of inhibition by calcitonin of phosphate reabsorption in the thyroparathyroidectomized rat. Pharmacologic doses of salmon calcitonin markedly inhibited fluid and phosphate reabsorption by the superficial proximal tubule. However, continued phosphate reabsorption between the superficial late proximal and early distal tubule, as well as along the distal tubule, blunted the phosphaturic effect of calcitonin. We conclude that the phosphaturic effect of a pharmacologic dose of salmon calcitonin is primarily due to an inhibition of fluid and phosphate reabsorption by the proximal convoluted tubule.

Transport of salicylate in proximal tubule (S2 segment) isolated from rabbit kidney

1988 ◽  
Vol 254 (4) ◽  
pp. F554-F561
Author(s):  
L. Schild ◽  
F. Roch-Ramel
Keyword(s):  
Proximal Tubule ◽  
Transport System ◽  
Concentration Gradient ◽  
Bath Temperature ◽  
Rabbit Kidney ◽  
Luminal Membrane ◽  
Carrier Mediated Transport ◽  
Secretory Transport ◽  
Luminal Ph

The secretory and reabsorptive transport of salicylate was studied in the isolated and perfused rabbit proximal tubule (S2 segment). Salicylate secretion (Jb----lsal) fulfilled the criteria for a carrier-mediated transport system: Jb----lsal was saturable, was reversibly inhibited by probenecid, and occurred against a concentration gradient. The Km and Vmax for this secretory transport were 80 microM and 3,200 fmol.min-1.mm-1, respectively. At luminal pH of 7.4 and 6.6, salicylate reabsorption (Jl----bsal) was low (100 fmol.min-1.mm-1). Jl----bsal was stimulated by increasing the bath PCO2 or by removing basolateral HCO3-; Jl----bsal was inhibited by ethoxyzolamide and by SITS in the bath. Our results indicate that salicylate reabsorption depends on H+ secretion, consistent with reabsorption by simple nonionic diffusion. When salicylate was present in the lumen only, Jl----bsal increased after inhibition of the secretory transport by adding ouabain or probenecid in the bath or by lowering the bath temperature. These results are compatible with luminal recycling of salicylate, and suggest the presence of a mediated secretory transporter located at the luminal membrane.

Nephron sites of action of nicotinamide on phosphate reabsorption

1984 ◽  
Vol 246 (1) ◽  
pp. F27-F31
Author(s):  
J. A. Haas ◽  
T. J. Berndt ◽  
A. Haramati ◽  
F. G. Knox
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Proximal Convoluted Tubule ◽  
Free Flow ◽  
Loop Of Henle ◽  
Phosphate Deprivation ◽  
Phosphate Reabsorption ◽  
Pars Recta ◽  
Sites Of Action

The administration of nicotinamide results in urinary phosphate excretions similar to those obtained with pharmacologic doses of parathyroid hormone (PTH). Free-flow micropuncture was performed to localize the nephron site(s) of inhibition of phosphate reabsorption by nicotinamide or PTH in thyroparathyroidectomized (TPTX) rats stabilized on a normal or low phosphate diet. In rats fed a normal phosphate diet phosphaturia was observed following either nicotinamide or PTH treatment. Nicotinamide inhibited phosphate reabsorption in the loop of Henle (pars recta) but not in the accessible proximal tubule. PTH inhibited phosphate reabsorption in both the accessible proximal tubule and the pars recta. In phosphate deprivation, the phosphaturic response to either nicotinamide or PTH was blunted. Although phosphate reabsorption was markedly inhibited in the accessible proximal tubule with both nicotinamide and PTH, subsequent reabsorption in the loop of Henle and distal tubule blunted the phosphaturia. We conclude that nicotinamide primarily inhibits phosphate reabsorption by the pars recta in rats fed a normal phosphate diet, whereas it inhibits phosphate reabsorption by the proximal convoluted tubule in rats fed a low phosphate diet. Furthermore, avid reabsorption of phosphate in the pars recta accounts for the resistance to the phosphaturic effect of nicotinamide or PTH seen in rats fed a low phosphate diet.

Effect of metabolic acidosis on glucose reabsorption in rats with acute hyperglycemia

1990 ◽  
Vol 68 (1) ◽  
pp. 79-83 ◽  
Author(s):  
P. O. Magner ◽  
M. L. Halperin
Keyword(s):  
Proximal Tubule ◽  
Fractional Excretion ◽  
Electrochemical Gradient ◽  
Osmotic Diuresis ◽  
Acute Hyperglycemia ◽  
Luminal Membrane ◽  
Glucose Reabsorption ◽  
Other Substances ◽  
Hyperglycemic Hyperosmolar Nonketotic Coma ◽  
Filtered Load

The rate of reabsorption of glucose in the kidney is a factor to consider with respect to the degree of hyperglycemia in poorly controlled diabetics. The rate of reabsorption of glucose in the proximal tubule is driven by the electrochemical gradient for sodium across the luminal membrane. This gradient in the proximal tubule is also used to reabsorb a number of other substances, quantitatively the most important being bicarbonate. We wished to explore the hypothesis that acidosis, by reducing the filtered load of bicarbonate and therefore the reabsorption of bicarbonate in the proximal tubule, might permit an increased rate of reabsorption of glucose. Hyperglycemia was induced in rats by the infusion of hypertonic glucose. Reabsorption of glucose was measured by clearance methods and factored for glomerular filtration rate (GFR), which has a direct effect on the reabsorption of glucose. The reabsorption of glucose was increased in the kidney when the reabsorption of bicarbonate in the proximal tubule was decreased by either HCl-induced acidosis or the administration of a carbonic anhydrase inhibitor. This effect was independent of a change in GFR and the fractional excretion of Na, factors that may also lead to changes in the reabsorption of glucose by the kidney.Key words: diabetes mellitus, hyperglycemic hyperosmolar nonketotic coma, diabetic ketoacidosis, proximal convoluted tubule, hyperglycemia, glucosuria, osmotic diuresis.

scholarly journals SGLT2 Inhibitors: Physiology and Pharmacology

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0002772021
Author(s):  
Ernest M Wright
Keyword(s):  
Proximal Tubule ◽  
Glycosylated Hemoglobin ◽  
Blood Stream ◽  
Sglt2 Inhibitors ◽  
Luminal Membrane ◽  
Glucose Reabsorption ◽  
Lower Plasma Glucose ◽  
Glomerular Filtrate ◽  
Glucose Excretion

SGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 grams (one mole) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream where they remain in in the circulation for hours. On glomerular filtration, they bind specifically to SGLT2 in the luminal membrane of the early proximal tubule to reduce glucose reabsorption by 50-60%. Because of glucose excretion, these drugs lower plasma glucose and glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. The drugs also protect against heart and renal failure. The aim of this review is to summarize what is currently known about the physiology of renal SGLTs and the pharmacology of SGLT drugs.

Reabsorption and secretion of alpha-ketoglutarate along the rat nephron: a micropuncture study

1985 ◽  
Vol 248 (3) ◽  
pp. F404-F412 ◽  
Author(s):  
B. Ferrier ◽  
M. Martin ◽  
G. Baverel
Keyword(s):  
Proximal Tubule ◽  
Progressive Increase ◽  
Proximal Convoluted Tubule ◽  
Loop Of Henle ◽  
Progressive Reduction ◽  
Acid Base ◽  
Luminal Membrane ◽  
Pars Recta ◽  
Micropuncture Study ◽  
Steady State Levels

The transport of alpha-ketoglutarate (alpha-KG) across the luminal membrane of the rat nephron was studied by micropuncture and microassay techniques. In normal and acidotic rats, approximately 75% of the filtered alpha-KG was reabsorbed in the proximal tubule and 20% in the pars recta and/or loop of Henle at endogenous plasma concentration of alpha-KG. A progressive elevation to steady-state levels of plasma alpha-KG resulted in a progressive reduction of the fractional reabsorption of alpha-KG in the proximal tubule as well as in a progressive increase in the fractional reabsorption of alpha-KG in the pars recta and/or loop of Henle. At plasma alpha-KG concentration 20-40 times above normal, reabsorption of alpha-KG was found to be limited by a maximal tubular capacity. In alkalotic rats, net secretion of alpha-KG in the early proximal convoluted tubule, net reabsorption in the remainder of the proximal convoluted tubule, and net secretion in the pars recta and/or loop of Henle were observed. These micropuncture data indicate that, depending on the acid-base conditions, net reabsorption or net secretion of alpha-KG may occur in at least two distinct sites along the rat nephron.

Glucose transporters of rat proximal tubule: differential expression and subcellular distribution

1992 ◽  
Vol 262 (5) ◽  
pp. F807-F812 ◽  
Author(s):  
J. H. Dominguez ◽  
K. Camp ◽  
L. Maianu ◽  
W. T. Garvey
Keyword(s):  
Proximal Tubule ◽  
Basolateral Membrane ◽  
Glucose Transporters ◽  
Axial Distribution ◽  
Western Blots ◽  
Glucose Flux ◽  
Glucose Reabsorption ◽  
Straight Tubules ◽  
Straight Segments ◽  
Rat Proximal Tubule

In the late proximal tubule, glucose reabsorption progressively lowers the concentration of luminal glucose, and concentrative glucose influx increases to ensure complete glucose reabsorption. The change in glucose influx is effected by luminal Na(+)-dependent glucose transporters (Na(+)-GLUT), which exhibit higher Na(+)-to-glucose stoichiometric ratios in the late proximal tubule. In this work, the corresponding changes in the axial distribution of basolateral glucose efflux transporters (GLUTs) were examined. mRNAs encoding high-affinity facilitative basolateral transporter GLUT1, low-affinity GLUT2, and apical Na(+)-GLUT were identified in mixed populations of proximal convoluted and straight tubules. The organization of the cognate proteins was also appraised on Western blots. GLUT1 was present in glomeruli, proximal convoluted, and straight tubules, GLUT2 was only expressed in the proximal convoluted tubule, and Na(+)-GLUT was present in both proximal convoluted and straight segments. GLUT1 and GLUT2 were confined to the basolateral membrane, whereas Na(+)-GLUT was preferentially localized to the brush-border membrane. These data are consistent with the idea that glucose influx in early and late proximal tubule is achieved through Na(+)-GLUT, that GLUT1 and GLUT2 are responsible for glucose efflux in the early proximal tubule, and that in the late proximal tubule, where transcellular glucose flux is lower, only GLUT1 mediates glucose efflux.

Nephron site of resistance to phosphaturic effect of PTH during respiratory alkalosis

1985 ◽  
Vol 249 (6) ◽  
pp. F919-F922 ◽  
Author(s):  
T. J. Berndt ◽  
F. G. Knox
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Respiratory Alkalosis ◽  
Proximal Convoluted Tubule ◽  
Phosphate Reabsorption ◽  
Hormone Administration ◽  
Pars Recta ◽  
Fractional Excretion Of Phosphate

This study was performed to evaluate the nephron site(s) responsible for the blunted phosphaturic effect of parathyroid hormone during respiratory alkalosis. In normocapnic thyroparathyroidectomized rats, parathyroid hormone administration markedly increased the fractional excretion of phosphate (FEp) from 2.1 +/- 0.5 to 36.6 +/- 5.0%. However, in the respiratory alkalotic rats, parathyroid hormone administration did not significantly increase the FEp (1.4 +/- 0.9 to 5.9 +/- 2.2%). This blunted phosphaturic response to parathyroid hormone was not due to a blunted inhibition of phosphate reabsorption by the superficial proximal tubule, since parathyroid hormone administration significantly increased the fractional delivery of phosphate (FDp) at the superficial late proximal tubule in both normal (25.3 +/- 3.0 to 36.2 +/- 3.8%, delta 10.9 +/- 3.2%) and respiratory alkalotic rats (12.2 +/- 3.1 to 30.3 +/- 4.9%, delta 18.0 +/- 4.7%). Parathyroid hormone administration significantly increased the FDp at the superficial early distal tubule from 9.3 +/- 3.9 to 38.7 +/- 7.4% (delta 29.4 +/- 5.1%) in normal rats and from 4.5 +/- 1.7 to 12.9 +/- 3.4% (delta 8.5 +/- 3.2%) in the respiratory alkalotic rats. We conclude that the blunted phosphaturic response to parathyroid hormone in respiratory alkalotic rats is not due to a blunted inhibition of phosphate reabsorption by the proximal convoluted tubule but is primarily due to enhanced reabsorption by the pars recta segment of the proximal tubule.

scholarly journals Acetate transport in the S3 segment of the rabbit proximal tubule and its effect on intracellular pH.

1988 ◽  
Vol 92 (3) ◽  
pp. 395-412 ◽  
Author(s):  
N L Nakhoul ◽  
W F Boron
Keyword(s):  
Acetic Acid ◽  
Proximal Tubule ◽  
Intracellular Ph ◽  
Acid Transport ◽  
Subsequent Removal ◽  
Luminal Membrane ◽  
A Value ◽  
All Solutions ◽  
S3 Segment ◽  
The One

We monitored intracellular pH (pHi) in isolated perfused S3 segments of the rabbit proximal tubule, and studied the effect of acetate (Ac-) transport on pHi. pHi was calculated from the absorbance spectrum of 4',5'-dimethyl-5-(and 6) carboxyfluorescein trapped intracellularly. All solutions were nominally HCO3(-)-free. Removal of 10 mM Ac- from bath and lumen caused pHi to rapidly rise by approximately 0.2, and then to decline more slowly to a value approximately 0.35 below the initial one. Removal of only luminal Ac- caused pHi changes very similar to those resulting from bilateral removal of Ac-. When Ac- was removed from bath only, pHi rose rapidly at first, and then continued to rise more slowly. Readdition of Ac- to bath caused pHi to rapidly fall to a value slightly higher than the one prevailing before the removal of Ac- from the bath. In experiments in which Ac- was first removed from both bath and lumen, readdition of 10 mM Ac- to only lumen caused a rapid but small acidification, followed by a slower alkalinization that brought the pHi near the value that prevailed before the bilateral removal of Ac-. The alkalinizing effects caused by the readdition of 10 or 0.5 mM Ac- were indistinguishable. When Ac- was returned to only lumen in the absence of luminal Na+, there was a small and rapid pHi decrease, but no pHi recovery. Removal of Na+ from bath did not affect the pHi transients caused by the addition of Ac- to lumen. In experiments in which Ac- was first removed bilaterally, readdition of Ac- to only bath caused a large and sustained drop in pHi, whereas the subsequent removal of Ac- from the bath caused a slight alkalinization. These pHi changes caused by readdition or removal of Ac- from baths were unaffected by the absence of external Na+. We conclude that there is a Na+/Ac- cotransporter at the luminal membrane, and pathways for acetic acid transport at both luminal and basolateral membranes. The net effect of Ac- transport on pHi is to alkalinize the cell as a result of the luminal entry of Na+/Ac-, which is followed by the luminal and basolateral exit of acetic acid.

Role of Na+/H+ exchanger NHE3 in nephron function: micropuncture studies with S3226, an inhibitor of NHE3

2000 ◽  
Vol 278 (3) ◽  
pp. F375-F379 ◽  
Author(s):  
Volker Vallon ◽  
Jan-Robert Schwark ◽  
Kerstin Richter ◽  
Max Hropot
Keyword(s):  
Proximal Tubule ◽  
Proximal Convoluted Tubule ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Luminal Membrane ◽  
Henle's Loop ◽  
Dependent Inhibition ◽  
Proximal Tubular ◽  
Dose Dependent Inhibition

Na+/H+ exchanger NHE3 is expressed in the luminal membrane of proximal tubule and thin and thick ascending limb of Henle's loop. To further define its role, the novel NHE3 inhibitor S3226 was employed in micropuncture experiments in nephrons with superficial glomeruli of anesthetized rats. Microperfusion of proximal convoluted tubule with S3226 revealed a dose-dependent inhibition of reabsorption (IC50 of 4–5 μM) with a maximum inhibition of 30% for fluid and Na+. During microperfusion of Henle's loop (last superficial proximal to first superficial distal tubular loop), no effect of S3226 (10 or 30 μM) on the reabsorption of fluid or Na+ was observed. Finally, S3226 (30 μM) left the tubuloglomerular feedback response unaltered as determined by the fall in proximal tubular stop-flow pressure in response to increasing loop of Henle perfusion rate. These studies indicate that NHE3 significantly contributes to fluid and Na+ reabsorption in proximal convoluted tubule. NHE3 appears not to significantly contribute to fluid or Na+reabsorption in the loop of Henle (including the S3 segment of proximal tubule) or macula densa control of nephron filtration.

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