Kidney Immunopathology and Pathophysiology in Rats Immunized with Proximal Tubule Cell Brush Border or Basolateral Membrane Vesicles

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.

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Na+-coupled bicarbonate transport in renal proximal tubular epithelia

Canadian Journal of Botany ◽

10.1139/b91-127 ◽

1991 ◽

Vol 69 (5) ◽

pp. 989-994 ◽

Cited By ~ 4

Author(s):

Steven M. Grassl

Keyword(s):

Proximal Tubule ◽

Basolateral Membrane ◽

Functional Characterization ◽

Membrane Vesicles ◽

Bicarbonate Transport ◽

Proximal Tubule Cell ◽

Acid Base Balance ◽

Tubule Cell ◽

Acid Base ◽

Transport Pathway

The renal proximal tubule cell is the functional unit of an epithelium that serves to maintain a normal acid–base balance by reclaiming HCO3− filtered at the glomerulus and returning it to the circulation. The proximal tubule cell performs transcellular HCO3− reabsorption by a process of H+ secretion at the luminal membrane and export of intracellular HCO3− at the basolateral membrane. The present review describes the identification and functional characterization of the major transport pathway mediating efflux of intracellular HCO3− across the basolateral membrane of the proximal tubule cell. Compelling experimental evidence obtained from investigations using isolated membrane vesicles and the perfused proximal tubule preparation is discussed that indicate this transport pathway is an electrogenic cotransport mechanism coupling transfer of Na+, HCO3−, and CO32− across the basolateral membrane. Key words: acid–base, bicarbonate reabsorption, renal epithelia.

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Characterization of sodium-dependent and sodium-independent nucleoside transport systems in rabbit brush-border and basolateral plasma-membrane vesicles from the renal outer cortex

Biochemical Journal ◽

10.1042/bj2640223 ◽

1989 ◽

Vol 264 (1) ◽

pp. 223-231 ◽

Cited By ~ 45

Author(s):

T C Williams ◽

A J Doherty ◽

D A Griffith ◽

S M Jarvis

Keyword(s):

Brush Border ◽

Basolateral Membrane ◽

Membrane Vesicles ◽

Nucleoside Transport ◽

Transport Systems ◽

Facilitated Diffusion ◽

Basolateral Membrane Vesicles ◽

Plasma Membrane Vesicles ◽

Outer Cortex ◽

Overshoot Phenomenon

The transport of uridine into rabbit renal outer-cortical brush-border and basolateral membrane vesicles was compared at 22 degrees C. Uridine was taken up into an osmotically active space in the absence of metabolism for both types of membrane vesicles. Uridine influx by brush-border membrane vesicles was stimulated by Na+, and in the presence of inwardly directed gradients of Na+ a transient overshoot phenomenon was observed, indicating active transport. Kinetic analysis of the saturable Na+-dependent component of uridine flux indicated that it was consistent with Michaelis-Menten kinetics (Km 12 +/- 3 microM, Vmax. 3.9 +/- 0.9 pmol/s per mg of protein). The sodium:uridine coupling stoichiometry was found to be consistent with 1:1 and involved the net transfer of positive charge. In contrast, uridine influx by basolateral membrane vesicles was not dependent on the cation present and was inhibited by nitrobenzylthioinosine (NBMPR). NBMPR-sensitive uridine transport was saturable (Km 137 +/- 20 microM, Vmax. 5.2 +/- 0.6 pmol/s per mg of protein). Inhibition of uridine flux by NBMPR was associated with high-affinity binding of NBMPR to the basolateral membrane (Kd 0.74 +/- 0.46 nM). Binding of NBMPR to these sites was competitively blocked by adenosine and uridine. These results indicate that uridine crosses the brush-border surface of rabbit proximal renal tubule cells by Na+-dependent pathways, but permeates the basolateral surface by NBMPR-sensitive facilitated-diffusion carriers.

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Na+-independent D-glucose transport in rabbit renal basolateral membranes

AJP Renal Physiology ◽

10.1152/ajprenal.1988.254.5.f711 ◽

1988 ◽

Vol 254 (5) ◽

pp. F711-F718 ◽

Cited By ~ 3

Author(s):

P. T. Cheung ◽

M. R. Hammerman

Keyword(s):

Glucose Uptake ◽

Glucose Transport ◽

Brush Border ◽

Glucose Transporter ◽

Cytochalasin B ◽

Basolateral Membrane ◽

Membrane Vesicles ◽

Rabbit Kidney ◽

Basolateral Membrane Vesicles ◽

Proximal Tubular

To define the mechanism by which glucose is transported across the basolateral membrane of the renal proximal tubular cell, we measured D-[14C]glucose uptake in basolateral membrane vesicles from rabbit kidney. Na+-dependent D-glucose transport, demonstrable in brush-border vesicles, could not be demonstrated in basolateral membrane vesicles. In the absence of Na+, the uptake of D-[14C]glucose in basolateral vesicles was more rapid than that of L-[3H]glucose over a concentration range of 1-50 mM. Subtraction of the latter from the former uptakes revealed a saturable process with apparent Km of 9.9 mM and Vmax of 0.80 nmol.mg protein-1.s-1. To characterize the transport component of D-glucose uptake in basolateral vesicles, we measured trans stimulation of 2 mM D-[14C]glucose entry in the absence of Na+. Trans stimulation could be effected by preloading basolateral vesicles with D-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose, but not with L-glucose or alpha-methyl-D-glucoside. Trans-stimulated D-[14C]glucose uptake was inhibited by 0.1 mM phloretin or cytochalasin B but not phlorizin. In contrast, Na+-dependent D-[14C]glucose transport in brush-border vesicles was inhibited by phlorizin but not phloretin or cytochalasin B. Our findings are consistent with the presence of a Na+-independent D-glucose transporter in the proximal tubular basolateral membrane with characteristics similar to those of transporters present in nonepithelial cells.

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