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-ketoglutarate effect on organic
anion secretion in perfused rabbit proximal tubules
Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona 85724
To determine the quantitative roles of the basolateral and
luminal Na+-dicarboxylate (Na-DC)
cotransporters in establishing and maintaining the
-ketoglutarate
(
KG) gradient required for renal tubular secretion of organic
anions, we measured net steady-state transepithelial secretion of
fluorescein (FL) in real time in isolated, perfused S2 segments of
rabbit renal proximal tubules. Net "basal" FL secretion in the
absence of exogenous
KG had a
Kt of ~4 µM
and a maximal transepithelial secretion rate
(Jmax) of
~380
fmol · min
1 · mm
1
(where Kt is the
FL concentration that produces one-half the Jmax).
It could be almost completely inhibited by basolateral p-aminohippurate (PAH). Selective
inhibition of the basolateral Na-DC cotransporter indicated that
recycling via this transporter of
KG that had been exchanged for FL
supports ~25% of the "basal" FL secretion. Physiological
KG
concentrations of 10 µM in the bath or 50 µM in the perfusate
stimulated net secretion of FL by ~30 or ~20%, respectively. These
data indicate that the basolateral Na-DC cotransporter supports ~42%
of the net FL secretion. The luminal and basolateral effects of
physiological concentrations of
KG were additive, indicating that
the combined function of the luminal and basolateral Na-DC
cotransporters can support ~50% of the net FL secretion. This
apparently occurs by their establishing and maintaining ~50% of the
outwardly directed
KG gradient that is responsible for driving
basolateral FL/
KG exchange. The remaining ~50% would be
maintained by metabolic production of
KG in the cells.
fluorescein; sodium-dicarboxylate cotransporters; transepithelial transport in real time
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