Effect of [alpha]kg in lumen on pah transport by isolated perfused
rabbit renal proximal tubules.
Dantzler, William H., and Kristen K. Evans.
Department of Physiology, College of Medicine, University of
Arizona, Tucson, Arizona 85724
APStracts 3:0076F, 1996.
To determine whether dicarboxylate taken up at the luminal membrane
could function in the p-aminohippurate (PAH) countertransport at the
basolateral membrane, we examined the effect of adding [alpha]
-ketoglutarate ([alpha]KG) or glutarate (a nonmetabolized
dicarboxylate that is countertransported for PAH at the basolateral
membrane) to the luminal perfusate on net secretion of radiolabeled
PAH in isolated perfused S2 segments of rabbit proximal tubules.
Addition of 100 [mu]M aKG or glutarate to the luminal perfusate in
tubules perfused and bathed with HEPES-buffered medium (in the
absence of bicarbonate, glycine, lactate, malate, and citrate)
produced a reversible 2-fold stimulation of net PAH transepithelial
secretion. Addition of 4 mM LiCl (an inhibitor of Na-dicarboxylate
transport that does not directly affect PAH transport) to the luminal
perfusate along with [alpha]KG eliminated stimulation of net PAH
secretion. Addition of 100 [mu]M or 1 mM [alpha]KG or glutarate to
the luminal perfusate in tubules perfused and bathed with
bicarbonate-buffered medium containing glycine, lactate, malate, and
citrate had no effect on net PAH transport from bath to lumen. These
data indicate that [alpha]KG (or glutarate) that enters the tubule
cells via the luminal Na-dicarboxylate cotransporter can stimulate
net PAH secretion, apparently via countertransport at the basolateral
membrane, but only when tubules are not in an optimal metabolic state
to produce intracellular [alpha]KG.
Received 7 August 1995; accepted in final form 4 April 1996.
APS Manuscript Number F259-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96