Renal handling of phenol red. IV. Tubular localization in rabbit and rat kidney in vivo

Sheikh, Mujeeb; Møller, Jesper

doi:10.1152/ajprenal.1980.238.3.f159

Cited by 4 publications

(2 citation statements)

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“…The most notable observation in their study was that the uptake of L-proline by these vesicles, in contrast with the uptake of the amino acid by membrane vesicles isolated from adult rats, did not show an overshoot. The apparent discrepancy between our experimental results and those obtained by Goldmann et al (1979) on the mechanism of uptake of proline by luminal-membrane vesicles derived from newborn animals may be due to species difference, since it has been reported that the tubular localization of Phenol Red in rat and rabbit kidney is basically different (Sheikh & M0ller, 1980). However, it seems reasonable to avoid further speculation on this before a more detailed study on the renal uptake of proline in newborn animals is provided.…”

Section: Resultscontrasting

confidence: 99%

An efficient method for the isolation and separation of basolateral-membrane and luminal-membrane vesicles from rabbit kidney cortex

Sheikh¹,

Kragh‐Hansen²,

Jørgensen³

et al. 1982

Biochemical Journal

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A procedure for isolation and separation of purified luminal-membrane and basolateral-membrane vesicles from adult and newborn rabbit renal cortex by using Ca2+/Mg2+ precipitation, differential centrifugation and a self-orienting Percoll-gradient centrifugation is described. The purity of the membrane-vesicle suspensions was examined by electron microscopy and by measuring the activity of several marker enzymes. The activity of Na+ + K+-stimulated ATPase in the fraction mainly containing adult rabbit basolateral-membrane vesicles was enriched 16-fold, and the activity of alkaline phosphatase in the fraction mainly containing luminal-membrane vesicles was increased 13-fold, compared with the homogenate. Similar results were obtained with kidneys from newborn rabbits. Uptake studies, with a rapid filtration technique and the spectrophotometric method described in an accompanying paper [Kragh-Hansen, Jørgensen & Sheikh (1982) Biochem. J. 208, 359-368], showed that both adult and newborn rabbit luminal-membrane vesicles, in contrast with the basolateral-membrane preparations, possess an Na+-dependent electrogenic transport system for L-proline. Adult rabbit luminal-membrane vesicles take up citrate and L-malate by Na+-dependent electrogenic processes, whereas adult rabbit basolateral membrane vesicles do not exhibit electrogenic uptake of citrate. By contrast, these vesicles show Na+-dependent electrogenic uptake of L-malate.

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Section: Resultscontrasting

confidence: 99%

An efficient method for the isolation and separation of basolateral-membrane and luminal-membrane vesicles from rabbit kidney cortex

Sheikh¹,

Kragh‐Hansen²,

Jørgensen³

et al. 1982

Biochemical Journal

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“…Nonetheless, phenol red clearance remained in use for many years as a test of renal function (19,20). High fractional clearance of protein-bound solutes like phenol red is achieved by active solute transport into the tubular lumen (21). Free solute levels in the renal interstitium are pumped down low enough so that a large portion of bound solute dissociates from plasma proteins during the few seconds that blood transits the kidney.…”

Section: Discussionmentioning

confidence: 99%

Increasing Dialysate Flow and Dialyzer Mass Transfer Area Coefficient to Increase the Clearance of Protein-bound Solutes

Meyer¹,

Leeper²,

Bartlett

et al. 2004

Journal of the American Society of Nephrology

102

116

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Abstract. Clinical hemodialysis systems achieve high single pass extraction of small solutes that are not bound to plasma proteins. But they clear protein-bound solutes much less effectively. This study examines the extent to which clearance of a protein-bound test solute is improved by increasing the dialyzer mass transfer area coefficient (K o A) and the dialysate flow rate (Q d Protein-bound solutes are poorly cleared during conventional hemodialysis (1-4). Accumulation of such solutes may contribute to residual uremic disorders when levels for dialytic clearance of urea and other small, unbound solutes are considered "adequate" (3-5). The dialytic clearance of an unbound solute is determined by the blood flow rate, Q b , the dialyzer mass transfer area coefficient, K o A, for that solute, and the dialysate flow rate, Q d (6). In conventional practice, K o A and Q d are set to achieve values for urea clearance close to Q b . Further increases in K o A and Q d cannot significantly increase urea clearance and are therefore generally not contemplated.The study presented here examined whether the clearance of protein-bound solutes could, by contrast, be improved by increasing K o A and Q d relative to the plasma flow rate, Q p . In vitro dialysis experiments measured the clearance of phenol red, a small solute strongly bound to albumin, from artificial plasma. As expected, the clearance of phenol red was much lower than the clearances of the unbound solutes, urea and creatinine. Phenol red clearance could, however, be increased by increasing both K o A and Q d . We developed a mathematical model to predict the clearance of a protein-bound solute from Q p , Q d , K o A, the albumin concentration, and the association constant, K A , that describes the strength of solute binding to albumin. Mathematical modeling accurately predicted the pattern of measured results and showed further that clearance values for tightly protein-bound solutes can be made to approach Q p by significantly increasing K o A and Q d . Materials and Methods Clearance Measurements during In Vitro DialysisModel Dialysis System. Clearances of phenol red, urea, and creatinine were measured during dialysis in vitro. Fluid representing a patient's plasma was placed in a continuously stirred 4.5 L reservoir and dialyzed with a Fresenius D machine (Fresenius, Gurnee, IL). The reservoir and dialysate fluids were prepared to have identical free electrolyte concentrations, which approximated Na 140 mEq/L, K 4.0 mEq/L, HCO 3 24 mEq/L, Mg 2.0 mEq/L, Ca 2.5 mEq/L, and PO 4 4.0 mg/dl. Fluid preparation comprised addition of small amounts of KCl, MgCl 2 , and CaCl 2 to Fresenius 6615 acid concentrate and NaH 2 PO 4 to 1.0 M NaHCO 3 concentrate solutions. These solutions were then mixed and appropriately diluted by the dialysis machine. Addition of reagent phenol red, urea, and creatinine to the reservoir provided concentrations of approximately 3.0 mg/dl, 120 mg/dl, and 12.0 mg/dl, respectively, at the beginning of each dialysis run. Dialysis experiments en...

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Physiologically based pharmacokinetic model for the renal clearance of phenolsulfonphthalein and the interaction with probenecid and salicyluric acid in the dog

Rüssel

Wouterse

Ginneken

1987

Journal of Pharmacokinetics and Biopharmaceutics

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Plasma kinetics and renal excretion of intravenous phenolsulfonphthalein (PSP, 1.0 g), with and without concomitant administration of probenecid or salicyluric acid (SUA), were studied in the Beagle dog. Pharmacokinetic analysis revealed that tubular secretion is the predominant route of excretion, and that secretion is inhibited by probenecid and SUA. A physiologically based kidney model was developed that incorporates the functional characteristics of the kidney that determine the excretion of PSP, i.e., renal plasma flow, urine flow, nonlinear protein binding, glomerular filtration, tubular secretion, and tubular accumulation. The model enabled an accurate description and analysis of the measured plasma levels and renal excretion rates. The interaction with probenecid and SUA could be adequately described with the model by inhibition of the carrier-mediated uptake of PSP into the proximal tubular cells. However, both compounds clearly differed in their inhibitory action. Whereas probenecid showed simple competitive inhibition, for SUA a considerably more complex interaction (two-site competitive system) had to be taken into consideration. Especially in the interaction experiments, only satisfactory fits to the model were obtained when secretion was assumed to be dependent on unbound PSP concentrations. Model calculations showed that in the control experiments tubular secretion was accompanied by a pronounced accumulation of PSP within the proximal tubular cells, which was clearly diminished in presence of probenecid or SUA. The predicted accumulation ratios were in good agreement with previous studies.

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Renal handling of phenol red. IV. Tubular localization in rabbit and rat kidney in vivo

Cited by 4 publications

References 0 publications

An efficient method for the isolation and separation of basolateral-membrane and luminal-membrane vesicles from rabbit kidney cortex

An efficient method for the isolation and separation of basolateral-membrane and luminal-membrane vesicles from rabbit kidney cortex

Increasing Dialysate Flow and Dialyzer Mass Transfer Area Coefficient to Increase the Clearance of Protein-bound Solutes

Physiologically based pharmacokinetic model for the renal clearance of phenolsulfonphthalein and the interaction with probenecid and salicyluric acid in the dog

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