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.

D-Glucose enhancement of water reabsorption in proximal tubule of the rat kidney

1976 ◽  
Vol 231 (3) ◽  
pp. 777-780 ◽  
Author(s):  
EJ Weinman ◽  
WN Suki ◽  
G Eknoyan
Keyword(s):  
Proximal Tubule ◽  
Rat Kidney ◽  
Specific Effect ◽  
Proximal Convoluted Tubule ◽  
Water Reabsorption ◽  
Perfusion Solution ◽  
Tubular Lumen ◽  
Artificial Solution

Water reabsorption in the proximal convoluted tubule of the rat kidney was examined by in vivo microperfusion techniques in order to examine the effect of D-glucose within the tubular lumen. When tubules were perfused with a balanced artificial solution containing Na, K, Cl, HCO3, urea, and D-glucose, absolute reabsorption averaged 4.01 +/- 0.24 nl/min per mm. Addition of D-glucose to the NaCl perfusate enhanced water reabsorption to values similar to those obtained with the balanced artificial perfusate. The enhanced water reabsorption consequent to the addition of D-glucose to the NaCl perfusion solution was completely inhibited by addition of phloridzin to the perfusate. The addition of an unabsorbed hexose, 2-deoxy-D-glucose, to the NaCl perfusate failed to enhance water reabsorption, whereas the addition of an incompletely reabsorbed sugar that is not metabolized, 3-O-methyl-D-glucose, resulted in partial enhancement of theabsolute rate of water reabsorption. These studies demonstrate that D-glucose has the specific effect of augmenting water reabsorption in the proximal tubule of the rat kidney.

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.

Secretion of urate in the proximal convoluted tubule of the rat

1980 ◽  
Vol 239 (4) ◽  
pp. F383-F387 ◽  
Author(s):  
E. J. Weinman ◽  
S. C. Sansom ◽  
D. A. Steplock ◽  
A. U. Sheth ◽  
T. F. Knight ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
High Performance ◽  
Competitive Inhibitor ◽  
Capillary Perfusion ◽  
Perfusion Solution ◽  
Organic Acid Secretion ◽  
Net Flux ◽  
Rat Proximal Tubule ◽  
Urate Secretion

In order to examine the transepithelial secretory flux of urate in the rat proximal tubule, simultaneous perfusions of capillaries and lumens were performed. The capillary perfusate contained [2–14C]urate in concentrations of 0.305–2.941 mM. The secretory flux of urate increased as the concentration of urate in the capillary perfusion solution was increased from 0.305 to 1.235 mM but tended toward a plateau at higher concentrations. An apparent Km of 0.41 mM and Vmax of 4.7 pmol·min-1·mm-1 were calculated from the observed net flux and an estimated passive permeability coefficient of 0.725 pmol·min-1·mm-1. The addition of probenecid (10-4 M) to the capillary perfusion solution inhibited urate secretion in a manner consistent with that of a competitive inhibitor. The addition of p-chloromercuribenzoate (10-4 M) to the capillary perfusion solution inhibited the Vmax but not the Km, suggesting a non-competitive type of inhibition. These data provide the first estimates of the apparent transport constants for urate secretion in the rat proximal tubule determined in vivo. Urate secretion is mediated by a saturable carrier-mediated system. This carrier is not affected by the presence or absence of potassium in the perfusion solution but can be inhibited by the addition of either probenecid or p-chloromercuribenzoate. high-performance liquid chromatography with electrochemical detection; renal micropunction; organic acid secretion Submitted on March 5, 1980 Accepted on April 25, 1980

Proximal tubule glucose efflux in the rat as a function of delivered load

1980 ◽  
Vol 238 (6) ◽  
pp. F499-F503 ◽  
Author(s):  
T. F. Knight ◽  
H. O. Senekjian ◽  
S. C. Sansom ◽  
E. J. Weinman
Keyword(s):  
Proximal Tubule ◽  
Glucose Concentration ◽  
Glucose Solution ◽  
Initial Glucose Concentration ◽  
Perfusion Solution ◽  
Glucose Flux ◽  
Flow Dependency ◽  
Absorptive Flux ◽  
Rat Proximal Tubule

The effect of altering the delivered load of glucose by either increasing the rate of perfusion or the initial glucose concentration on the absorptive flux of glucose was examined in rat proximal tubule using the in vivo microperfusion technique. The passive flux coefficient was determined to be 1.27 pmol . min-1 . mm-1 . mM-1 glucose concentration gradient. With initial glucose concentrations of either 11.1 or 22.2 mM, the glucose flux increased as the rate of perfusion was increased. At similar rates of perfusion, glucose flux was higher from 22.2 mM glucose solution than from the 11.1 mM solution. Estimation of the driving force for passive glucose efflux indicates that the increase in glucose efflux when flow rate is increased cannot be accounted for by passive changes in efflux out of the proximal tubule. When large transepithelial glucose gradients are imposed across the tubule, passive glucose flux plays a more significant role, but cannot totally account for higher rates of glucose efflux observed with the perfusion solution containing 22.2 mM glucose. These results are considered in light of the recent model of the flow dependency of nonelectrolyte absorption of Barfuss and Schafer [Am. J. Physiol. 236 (Renal Fluid Electrolyte Physiol. 5): F163–F174. 1979].

The Fine Structure of Rat Renal Microbodies and Cytoplasmic Bodies Following Perfusion Fixation

1973 ◽  
Vol 31 ◽  
pp. 620-621
Author(s):  
J. M. Barrett ◽  
P. M. Heidger
Keyword(s):  
Fine Structure ◽  
Proximal Tubule ◽  
Rat Kidney ◽  
Renal Proximal Tubule ◽  
Convincing Evidence ◽  
Cytoplasmic Bodies ◽  
Rat Renal Proximal Tubule ◽  
Renal Proximal Tubule Cells ◽  
Perfusion Fixation

Microbodies have received extensive morphological and cytochemical investigation since they were first described by Rhodin in 1954. To our knowledge, however, all investigations of microbodies and cytoplasmic bodies of rat renal proximal tubule cells have employed immersion fixation. Tisher, et al. have shown convincing evidence of fine structural alteration of microbodies in rhesus monkey kidney following immersion fixation; these alterations were not encountered when in vivo intravascular perfusion was employed. In view of these studies, and the fact that techniques for perfusion fixation have been established specifically for the rat kidney by Maunsbach, it seemed desirable to employ perfusion fixation to study the fine structure and distribution of microbodies and cytoplasmic bodies within the rat renal proximal tubule.

Dependence of ion fluxes on fluid transport by rat proximal tubule

1986 ◽  
Vol 250 (4) ◽  
pp. F680-F689 ◽  
Author(s):  
K. Bomsztyk ◽  
F. S. Wright
Keyword(s):  
Proximal Tubule ◽  
Fluid Transport ◽  
Rat Kidney ◽  
Water Flux ◽  
Fluid Secretion ◽  
Proximal Convoluted Tubule ◽  
Ion Fluxes ◽  
Fluid Absorption ◽  
Fluid Flux ◽  
K Transport

The effects of changes in transepithelial water flux (Jv) on sodium, chloride, calcium, and potassium transport by the proximal convoluted tubule were examined by applying a microperfusion technique to surface segments in kidneys of anesthetized rats. Perfusion solutions were prepared with ion concentrations similar to those in fluid normally present in the later parts of the proximal tubule. Osmolality of the perfusate was adjusted with mannitol. With no mannitol in the perfusates, net fluid absorption was observed. Addition of increasing amounts of mannitol first reduced Jv to zero and then reversed net fluid flux. At the maximal rates of fluid absorption, net absorption of Na, Cl, Ca, and K was observed. When Jv was reduced to zero, Na, Cl, and Ca absorption were reduced and K entered the lumen. Na, Cl, and Ca secretion occurred in association with the highest rates of net fluid secretion. The lumen-positive transepithelial potential progressively increased as the net fluid flux was reduced to zero and then reversed. The results demonstrate that changes in net water flux can affect Na, Cl, Ca, and K transport by the proximal convoluted tubule of the rat kidney. These changes in net ion fluxes are not entirely accounted for by changes in bulk-phase transepithelial electrochemical gradients.

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.

Direct action of aldosterone on bicarbonate reabsorption in in vivo cortical proximal tubule

2009 ◽  
Vol 296 (5) ◽  
pp. F1185-F1193 ◽  
Author(s):  
Patricia Silva Pergher ◽  
Deise Leite-Dellova ◽  
Margarida de Mello-Aires
Keyword(s):  
Proximal Tubule ◽  
Direct Action ◽  
Rat Kidney ◽  
Free Calcium ◽  
Mineralocorticoid Receptor Antagonist ◽  
Control Value ◽  
Bicarbonate Reabsorption ◽  
Peritubular Capillaries ◽  
Inhibitor Of Protein Synthesis

The direct action of aldosterone (10−12 M) on net bicarbonate reabsorption ( JHCO3−) was evaluated by stationary microperfusion of an in vivo middle proximal tubule (S2) of rat kidney, using H ion-sensitive microelectrodes. Aldosterone in luminally perfused tubules caused a significant increase in JHCO3− from a mean control value of 2.84 ± 0.08 [49/19 ( n° of measurements/ n° of tubules)] to 4.20 ± 0.15 nmol·cm−2·s−1 (58/10). Aldosterone perfused into peritubular capillaries also increased JHCO3−, compared with basal levels during intact capillary perfusion with blood. In addition, in isolated perfused tubules aldosterone causes a transient increase of cytosolic free calcium ([Ca2+]i), monitored fluorometrically. In the presence of ethanol (in similar concentration used to prepare the hormonal solution), spironolactone (10−6 M, a mineralocorticoid receptor antagonist), actinomycin D (10−6 M, an inhibitor of gene transcription), or cycloheximide (40 mM, an inhibitor of protein synthesis), the JHCO3− and the [Ca2+]i were not different from the control value; these drugs also did not prevent the stimulatory effect of aldosterone on JHCO3− and on [Ca2+]i. However, in the presence of RU 486 alone [10−6 M, a classic glucocorticoid receptor (GR) antagonist], a significant decrease on JHCO3− and on [Ca2+]i was observed; this antagonist also inhibited the stimulatory effect of aldosterone on JHCO3− and on [Ca2+]i. These studies indicate that luminal or peritubular aldosterone (10−12 M) has a direct nongenomic stimulatory effect on JHCO3− and on [Ca2+]i in proximal tubule and that probably GR participates in this process. The data also indicate that endogenous aldosterone stimulates JHCO3− in middle proximal tubule.

Internalization and intracellular transport of folate-binding protein in rat kidney proximal tubule

1993 ◽  
Vol 264 (2) ◽  
pp. C302-C310 ◽  
Author(s):  
H. Birn ◽  
J. Selhub ◽  
E. I. Christensen
Keyword(s):  
Plasma Membrane ◽  
Proximal Tubule ◽  
Brush Border ◽  
Intracellular Transport ◽  
Brush Border Membrane ◽  
Specific Binding ◽  
Binding Protein ◽  
Rat Kidney ◽  
Folate Binding Protein

Folate-binding protein (FBP) is involved in folate reabsorption in the renal proximal tubule. Immunocytochemical studies have located FBP to the brush-border membrane, endocytic vacuoles, and dense apical tubules. We applied the same polyclonal antibody (anti-FBP) against FBP to investigate the dynamic relationship between FBP in the different compartments by microinjecting the antibody into rat kidney proximal tubules in situ. Specific binding of anti-FBP in vivo to the brush-border membrane was followed by fixation at various times. Protein A-gold labeling shows that anti-FBP is transported from endocytic invaginations into vacuoles followed by transport into dense apical tubules within 15 s. Thus FBP is rapidly internalized, and together with previous studies this study strongly suggests recycling of FBP back to the luminal plasma membrane through dense apical tubules. The results are consistent with reabsorption of folate through endocytosis of the FBP-folate complex followed by dissociation and recycling of FBP. When time is allowed there is a steady accumulation of FBP in dense apical tubules combined with an increase in surface density of the same compartment. A possible explanation involves partial inhibition of the fusion between dense apical tubules and plasma membrane because of the anti-FBP labeling of the receptor.

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