Transport by epithelia with compliant lateral intercellular spaces: asymmetric oncotic effects across the rat proximal tubule

1984 ◽  
Vol 247 (5) ◽  
pp. F848-F862 ◽  
Author(s):  
A. M. Weinstein
Keyword(s):  
Reflection Coefficient ◽  
Proximal Tubule ◽  
Electrical Resistance ◽  
Volume Flow ◽  
Intercellular Spaces ◽  
Water Reabsorption ◽  
Solute Permeability ◽  
Lateral Intercellular Spaces ◽  
Rat Proximal Tubule

Mathematical models of the proximal tubule are considered in which the lateral intercellular spaces distend in response to increased interstitial pressures and basal outlet permeabilities increase as a result of interspace widening. An approximate analytical model of the interspace reveals the possibility that such compliance may introduce an asymmetry to the effect of protein oncotic forces on transepithelial volume flow. Peritubular oncotic forces close the interspace, enhance interspace hypertonicity, and thus substantially increase volume reabsorption (enhanced intraepithelial solute-solvent coupling). The model also predicts a decline in epithelial water permeability (Lp), salt reflection coefficient, and salt permeability, with the application of peritubular protein. When parameters are chosen so as to represent the rat proximal tubule, the predicted effect on solute permeability is comparable to the observed changes in electrical resistance of the epithelium. However, when the luminal solution is slightly hypotonic to blood and proximal reabsorption has become isosmotic, the models show relatively small protein effects, which are dependent upon cell and tight junction permeabilities and are little influenced by interspace compliance. The capability of such models to represent the peritubular protein enhancement of isosmotic salt and water reabsorption by the proximal tubule in vivo is questioned.

Urate transport in the proximal tubule: in vivo and vesicle studies

1985 ◽  
Vol 249 (6) ◽  
pp. F789-F798 ◽  
Author(s):  
A. M. Kahn ◽  
E. J. Weinman
Keyword(s):  
Proximal Tubule ◽  
Brush Border ◽  
Anion Exchanger ◽  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Transport Processes ◽  
Basolateral Membrane Vesicles ◽  
Urate Transport ◽  
Rat Proximal Tubule

The transport of urate in the mammalian nephron is largely confined to the proximal tubule. Depending on the species, net reabsorption or net secretion is observed. The rat, like the human and the mongrel dog, demonstrates net reabsorption of urate and has been the most extensively studied species. The unidirectional reabsorption and secretion of urate in the rat proximal tubule occur via a passive and presumably paracellular route and by a mediated transcellular route. The reabsorption of urate, and possibly its secretion, can occur against an electrochemical gradient. A variety of drugs and other compounds affect the reabsorption and secretion of urate. The effects of these agents depend on their site of application (luminal or blood), concentration, and occasionally their participation in transport processes that do not have affinity for urate. Recent studies with renal brush border and basolateral membrane vesicles from the rat and brush border vesicles from the dog have determined the mechanisms for urate transport across the luminal and antiluminal membranes of the proximal tubule cell. Brush border membrane vesicles contain an anion exchanger with affinity for urate, hydroxyl ion, bicarbonate, chloride, lactate, p-aminohippurate (PAH), and a variety of other organic anions. Basolateral membrane vesicles contain an anion exchanger with affinity for urate and chloride but not for PAH. Both membrane vesicle preparations also permit urate translocation by simple diffusion. A model for the transcellular reabsorption and secretion of urate in the rat proximal tubule is proposed. This model is based on the vesicle studies, and it can potentially explain the majority of urate transport data obtained with in vivo techniques.

Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors

2004 ◽  
Vol 287 (4) ◽  
pp. F789-F796 ◽  
Author(s):  
Matthew A. Bailey
Keyword(s):  
Protein Kinase ◽  
Proximal Tubule ◽  
Ph Value ◽  
Receptor Activation ◽  
Ringer Solution ◽  
Dependent Manner ◽  
Bicarbonate Reabsorption ◽  
Mrs 2179 ◽  
Rat Proximal Tubule

The present study used a stationary microperfusion technique to investigate in vivo the effect of P2Y1 receptor activation on bicarbonate reabsorption in the rat proximal tubule. Proximal tubules were perfused with a bicarbonate Ringer solution before flow was stopped by means of an oil block. The recovery of lumen pH from the initial value (pH 8.0) to stationary values (pH ∼6.7) was recorded by a H+-sensitive microelectrode inserted downstream of the perfusion pipette and oil block. The stationary pH value and the t of pH recovery were used to calculate bicarbonate reabsorption ( JHCO3). Both EIPA and bafilomycin A1 caused significant reductions in proximal tubule JHCO3, consistent with the established contributions of Na/H exchange and H+-ATPase to proximal tubule HCO3 reabsorption. The nucleotides ADP and, to a lesser extent, ATP reduced JHCO3 but AMP and UTP were without effect. 2MeSADP, a highly selective agonist of the P2Y1 receptor, reduced JHCO3 in a dose-dependent manner. MRS-2179, a P2Y1 receptor-specific antagonist, abolished the effect of 2MeSADP, whereas theophylline, an antagonist of adenosine (P1) receptors, did not. The inhibitory action of 2MeSADP was blocked by inhibition of protein kinase C and reduced by inhibition of protein kinase A. The effects of EIPA and 2MeSADP were not additive. The data provide functional evidence for P2Y1 receptors in the apical membrane of the rat proximal tubule: receptor activation impairs acidification in this nephron segment.

scholarly journals Low salt intake increases adenosine type 1 receptor expression and function in the rat proximal tubule

2008 ◽  
Vol 295 (1) ◽  
pp. F37-F41 ◽  
Author(s):  
Aaron Kulick ◽  
Carolina Panico ◽  
Pritmohinder Gill ◽  
William J. Welch
Keyword(s):  
Proximal Tubule ◽  
Salt Intake ◽  
Selective Inhibitor ◽  
Receptor Expression ◽  
Local Production ◽  
Low Salt ◽  
And Function ◽  
Rat Proximal Tubule

Adenosine mediates Na+ reabsorption in the proximal tubule (PT) and other segments by activating adenosine type 1 receptors (A1-AR). We tested the hypothesis that A1-AR in the PT is regulated by salt intake and participates in the kidney adaptation to changes in salt intake. Absolute fluid reabsorption ( Jv) was measured by direct in vivo microperfusion and recollection in rats maintained on low (LS; 0.03% Na, wt/wt)-, normal (NS; 0.3% Na)-, and high-salt (HS; 3.0% Na) diets for 1 wk. The effect of microperfusion of BG9719 a highly selective inhibitor of A1-ARs or adenosine deaminase (AD), which metabolizes adenosine, was measured in each group. Jv was higher in PT from LS rats (LA: 2.8 ± 0.2 vs. NS: 2.1 ± 0.2 nl·min−1·mm−1, P < 0.001). Jv in HS rats was not different from NS. BG9719 reduced Jv in LS rats by 66 ± 6% (LS: 2.8 ± 0.2 vs LS+CVT: 1.3 ± 0.3 nl·min−1·mm−1, P < 0.001), which was greater than its effect in NS (45 ± 4%) or HS (41 ± 4%) rats. AD reduced Jv similarly, suggesting that A1-ARs are activated by local production of adenosine. Expression of A1-AR mRNA and protein was higher ( P < 0.01) in microdissected PTs in LS rats compared with NS and HS. We conclude that A1-ARs in the PT are increased by low salt intake and that A1-AR participates in the increased PT reabsorption of solute and fluid in response to low salt intake.

Effect of hypermagnesemia on rat jejunal sodium and water transport

1976 ◽  
Vol 231 (6) ◽  
pp. 1771-1776 ◽  
Author(s):  
GF DiBona ◽  
LL Sawin
Keyword(s):  
Proximal Tubule ◽  
Water Transport ◽  
Renal Proximal Tubule ◽  
Epithelial Tissue ◽  
Rat Jejunum ◽  
Water Reabsorption ◽  
Sodium Influx ◽  
Sodium Efflux ◽  
Rat Renal Proximal Tubule

Hypermagnesemia decreases sodium and water reabsorption in the rat renal proximal tubule. To further understand this action, the effect of hypermagnesemia on sodium and water transport in the in vivo perfused rat jejunum was studied. The rat jejunum was chosen as another transporting epithelial tissue in the same species with unidirectional sodium flux characteristics similar to the rat renal proximal tubule, i.e., leaky as opposed to tight. Hypermagnesemia decreased net jejunal sodium and water reabsorption. This decrease was due to a reduction in unidirectional sodium efflux from lumen to blood and not to an increase in unidirectional sodium influx from blood to lumen. Hypermagnesemia did not change the jejunal permeability to inulin. The effect of hypermagnesemia on jejunal sodium and water transport is similar to that renal proximal tubule sodium and water transport. This similarity suggests that the mechanism of action of magnesium of these two transporting epithelial tissues is similar.

Determination of the apparent transport constants for urate absorption in the rat proximal tubule

1981 ◽  
Vol 240 (5) ◽  
pp. F406-F410
Author(s):  
S. C. Sansom ◽  
H. O. Senekjian ◽  
T. F. Knight ◽  
H. Babino ◽  
D. Steplock ◽  
...  
Keyword(s):  
Reflection Coefficient ◽  
Proximal Tubule ◽  
Continuous Flow ◽  
Active Component ◽  
Solvent Drag ◽  
Perfusion Solution ◽  
Saturation Kinetics ◽  
Rat Proximal Tubule ◽  
Independent Confirmation

Using continuous-flow luminal microperfusion techniques, the influence of the intraluminal urate concentration on urate absorption was determined in the rat proximal tubule. When the estimated contribution of passive permeation was accounted for, the “active” component of urate absorption demonstrated saturation kinetics. The apparent Km was 0.17 mM and the Vmax 0.31 pmol.min-1.mm-1. These transport constants were similar when derived from either a water-absorbing or steady-state equilibrium perfusion solution. The reflection coefficient was determined in studies employing the techniques of simultaneous capillary and luminal microperfusion. Both perfusion solutions contained p-chloromercuribenzoate to inhibit active urate transport. In the presence or absence of an osmole gradient imposed across the tubule, the reflection coefficient for urate averaged 0.94. These studies provide evidence that urate absorption in the rat proximal tubule is a carrier-mediated process. They also provide independent confirmation of the passive flux coefficient derived in prior studies. Finally, the results suggest that solvent drag would have little effect on urate absorption.

Effects of intraluminal D-glucose and probenecid on urate absorption in the rat proximal tubule

1979 ◽  
Vol 236 (6) ◽  
pp. F526-F529 ◽  
Author(s):  
T. F. Knight ◽  
H. O. Senekjian ◽  
S. Sansom ◽  
E. J. Weinman
Keyword(s):  
Proximal Tubule ◽  
Water Absorption ◽  
Rat Kidney ◽  
Proximal Convoluted Tubule ◽  
Perfusion Solution ◽  
Hexose Sugars ◽  
Tubular Absorption ◽  
Rat Proximal Tubule ◽  
Fractional Absorption

The in vivo microperfusion technique was employed to examine urate absorption in the proximal convoluted tubule of the rat kidney using [2–14C]urate as the marker for fractional urate absorption. With NaCl as the perfusion solution, water absorption averaged 2.53 +/- 0.16 nl.min-1.mm tubule-1, and the fractional absorption of [2–14C]urate averages 11.6 +/- 1.0%/mm tubule. The addition of D-glucose (50 mg/100 ml) enhanced water absorption to 3.62 +/- 0.19 nl.min-1.mm tubule-1, but inhibited fractional urate absorption to 6.6 +/- 1.2%/mm tubule. Phloridzin (4.4 mg/100 ml), 2-deoxy-D-glucose (45.6 mg/100 ml), and 3-O-methyl-D-glucose (53.9 mg/100 ml) also inhibited the absorption of [2–14C]urate to the same degree as did D-glucose despite differing effects on water absorption. The addition of probenecid (2.8 mg/100 ml) to the NaCl perfusion solution had no effect on water absorption but inhibited [2–14C]urate absorption to 6.4 +/- 0.6%/mm tubule. The addition of both probenecid and phloridzin further reduced [2–14C-A1urate absorption to 3.8 +/- 0.7%/mm tubule. Probenecid alone had no effect on glucose transport. These studies suggest that the presence of either certain hexose sugars, phloridzin, or probenecid in the lumen of the proximal convoluted tubule inhibits the tubular absorption of urate.

Direct evaluation of the permeability of the rat proximal convoluted tubule to CO2

1982 ◽  
Vol 242 (5) ◽  
pp. F470-F476
Author(s):  
M. S. Lucci ◽  
L. R. Pucacco ◽  
N. W. Carter ◽  
T. D. DuBose
Keyword(s):  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Carbonic Acid ◽  
Carbonic Anhydrase Activity ◽  
Proximal Convoluted Tubule ◽  
Direct Evaluation ◽  
Carbon Dioxide Gas ◽  
Peritubular Capillaries ◽  
Rat Proximal Tubule

Conflicting data exist regarding the ability of the rat proximal convoluted tubule to maintain a transepithelial gradient for CO2 and the effects of carbonic anhydrase on CO2 permeability. The present in vivo microperfusion experiments were designed to assess the ability of the rat proximal tubule to sustain a CO2 gradient between tubule lumen and peritubular blood. Tubules were perfused at rates ranging from 10 to 100 nl/min with isotonic sodium chloride containing no CO2. Peritubular capillary and intraluminal PCO2 was measured during microperfusion with PCO2 microelectrodes to allow determination of the transepithelial CO2 gradient. The mean PCO2 measured in peritubular capillaries of control rats was 60.6 +/- 1.9 mmHg. Since the perfusion solution initially contained no CO2, a gradient of 60 mmHg was imposed across the tubule epithelium. Intraluminal PCO2 rapidly approached that of the surrounding capillaries. At a tubule perfusion rate of 20 nl/min, the gradient between lumen and blood decreased to 0.9 mmHg, a value not significantly greater than zero. The calculated CO2 permeability coefficient (KCO2) was 3.69 X 10(-5) cm2/s. Addition of either 10(-4) M acetazolamide or benzolamide did not prolong the rapid dissipation of the imposed CO2 gradient. The KCO2 during carbonic anhydrase inhibition was not significantly different from control values. It is concluded that the rat proximal tubule does not present a physiologically significant diffusion barrier to CO2 either in the presence or absence of carbonic anhydrase activity. The previously demonstrated acid disequilibrium pH in the proximal tubule during inhibition of carbonic anhydrase represents an intraluminal accumulation of carbonic acid rather than of carbon dioxide gas.

Ammonia entry along rat proximal tubule in vivo: effects of luminal pH and flow rate

1987 ◽  
Vol 253 (4) ◽  
pp. F760-F766 ◽  
Author(s):  
E. E. Simon ◽  
L. L. Hamm
Keyword(s):  
Proximal Tubule ◽  
Flow Rate ◽  
Ammonia Concentration ◽  
Bicarbonate Concentration ◽  
Perfusion Rate ◽  
Total Ammonia ◽  
Luminal Ph ◽  
In Vivo Effects ◽  
Rat Proximal Tubule

The roles of luminal pH and flow rate in determining ammonia entry along the rat proximal tubule were examined using in vivo microperfusion. With perfusion rate constant at 15 nl/min, perfusate bicarbonate concentration was varied. Collected fluid ammonia concentration correlated with collected fluid bicarbonate concentration, consistent with nonionic diffusion (r = 0.726; P less than 0.001). Hence ammonia entry was dependent on luminal pH. With perfusate bicarbonate constant at 5 or 25 mM, perfusion rate was varied. In all groups, there was little change in collected fluid ammonia concentration with flow rate. Thus ammonia entry was also highly dependent on flow rate. With paired collections using a 25 mM bicarbonate perfusate, collected fluid bicarbonate was higher at a 30 nl/min perfusion rate than at 15 nl/min (16.8+/- 1.1 vs. 10.3+/- 1.1 mM), whereas total ammonia concentrations were similar (0.54+/- 0.1 and 0.55+/- 0.1). Thus the NH3 concentration was higher at 30 than at 15 nl/min (6.1+/- 1.2 vs. 3.4+/- 0.5 microM; P less than 0.025), a result not predicted by simple nonionic diffusion. Thus these studies demonstrate the importance of nonionic diffusion in determining ammonia entry along the proximal tubule. However, the results also demonstrate that flow rate importantly determines ammonia entry in vivo in a manner not predicted by simple nonionic diffusion of NH3. This augmentation of ammonia entry with increasing flow rate may involve flow-dependent alterations in ammonia synthesis or transport of NH+4.

Pathways for apical and basolateral membrane NH3 and NH4+ movement in rat proximal tubule

1990 ◽  
Vol 259 (4) ◽  
pp. F587-F593 ◽  
Author(s):  
P. A. Preisig ◽  
R. J. Alpern
Keyword(s):  
Proximal Tubule ◽  
Apical Membrane ◽  
Basolateral Membrane ◽  
Basolateral Membranes ◽  
Ammonia Addition ◽  
Rat Proximal Tubule

To examine the mechanism of preferential luminal ammonia secretion in the proximal tubule the apical and basolateral membrane pathways for NH3 and NH4+ movement were studied in the in vivo microperfused rat proximal tubule. Na and Cl were absent from all perfusates. Changes in pHi in response to rapid addition of NH3-NH4+ to either the luminal or peritubular perfusates were measured microfluorimetrically and expressed as the H(+)-equivalent flux (JeqH in pmol.mm-1.min-1). After ammonia addition ([NH3] 0.3 mM; [NH4+] 14.7 mM) to the luminal or peritubular fluids, pHi increased, and JeqH = 1,713 +/- 181 and 1,040 +/- 132 pmol.mm-1.min-1, respectively. To determine whether the above difference was due to NH3- or NH4(+)-driven fluxes, the effect of a fivefold greater [NH4+] ([NH3] 0.3 mM; [NH4+] 74.5 mM) on JeqH was examined. With luminal addition of a fivefold greater [NH4+], JeqH increased to 3,299 +/- 292 pmol.mm-1.min-1, demonstrating a pathway for NH4(+)-driven H+ efflux. One millimolar luminal amiloride inhibited JeqH in response to luminal NH3-NH4+ addition, suggesting that the amiloride-sensitive Na(+)-H+ antiporter mediates the NH4(+)-driven H+ efflux. JeqH was unaffected by addition of a fivefold greater [NH4+] to the peritubular perfusate, demonstrating the absence of an NH4(+)-driven H+ flux on the basolateral membrane. From these data, the calculated NH3 permeabilities were 6.2 +/- 1.3 and 7.0 +/- 0.9 X 10(-2) cm/s for the apical and basolateral membranes, respectively (NS). We conclude that apical and basolateral membrane NH3 permeabilities are similar and large. The apical membrane can also transport NH4+ on the amiloride-sensitive Na(+)-H+ antiporter.

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