PAH/α-KG countertransport stimulates PAH uptake and net secretion in isolated rabbit renal tubules

Varanuj Chatsudthipong, William H Dantzler

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Abstract

Possible stimulation of both basolateral uptake and net transepithelial secretion of p-aminohippurate (PAH) by PAH/α-ketoglutarate (α-KG) countertransport was examined in intact perfused and nonperfused rabbit proximal S2 renal tubules. Preloading tubules with α-KG (100 μM) for 30 min increased [14C]-PAH rate of uptake by nonperfused tubules and rate of net secretion by perfused tubules approximately three- to sixfold. During stimulation of net secretion, intracellular [14C]PAH concentration increased to about the same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na+-dicarboxylate cotransport) in bathing medium during α-KG preloading eliminated stimulation of PAH transport. Addition of unlabeled α-KG (1 mM) to bathing medium stimulated efflux of [14C]PAH across the basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH/ α-KG countertransport. Preloading with succinate (100 μM) also stimulated rates of [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only ∼1.5-fold. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate [14C]PAH uptake by nonperfused tubules or net secretion by perfused tubules. Thus it seems most likely that succinate preloading stimulates PAH transport via metabolism, possibly by conversion to α-KG, not by direct countertransport for PAH. This study indicates for the first time in intact mammalian proximal S2 renal tubules that PAH/α-KG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume263
Issue number3 32-3
StatePublished - Sep 1992

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p-Aminohippuric Acid
Rabbits
Kidney
Succinic Acid
Proximal Kidney Tubule

Keywords

  • Dicarboxylate/organic anion countertransport
  • Organic anion transport
  • Succinate

ASJC Scopus subject areas

  • Physiology

Cite this

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title = "PAH/α-KG countertransport stimulates PAH uptake and net secretion in isolated rabbit renal tubules",
abstract = "Possible stimulation of both basolateral uptake and net transepithelial secretion of p-aminohippurate (PAH) by PAH/α-ketoglutarate (α-KG) countertransport was examined in intact perfused and nonperfused rabbit proximal S2 renal tubules. Preloading tubules with α-KG (100 μM) for 30 min increased [14C]-PAH rate of uptake by nonperfused tubules and rate of net secretion by perfused tubules approximately three- to sixfold. During stimulation of net secretion, intracellular [14C]PAH concentration increased to about the same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na+-dicarboxylate cotransport) in bathing medium during α-KG preloading eliminated stimulation of PAH transport. Addition of unlabeled α-KG (1 mM) to bathing medium stimulated efflux of [14C]PAH across the basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH/ α-KG countertransport. Preloading with succinate (100 μM) also stimulated rates of [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only ∼1.5-fold. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate [14C]PAH uptake by nonperfused tubules or net secretion by perfused tubules. Thus it seems most likely that succinate preloading stimulates PAH transport via metabolism, possibly by conversion to α-KG, not by direct countertransport for PAH. This study indicates for the first time in intact mammalian proximal S2 renal tubules that PAH/α-KG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.",
keywords = "Dicarboxylate/organic anion countertransport, Organic anion transport, Succinate",
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year = "1992",
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volume = "263",
journal = "American Journal of Physiology",
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T1 - PAH/α-KG countertransport stimulates PAH uptake and net secretion in isolated rabbit renal tubules

AU - Chatsudthipong, Varanuj

AU - Dantzler, William H

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N2 - Possible stimulation of both basolateral uptake and net transepithelial secretion of p-aminohippurate (PAH) by PAH/α-ketoglutarate (α-KG) countertransport was examined in intact perfused and nonperfused rabbit proximal S2 renal tubules. Preloading tubules with α-KG (100 μM) for 30 min increased [14C]-PAH rate of uptake by nonperfused tubules and rate of net secretion by perfused tubules approximately three- to sixfold. During stimulation of net secretion, intracellular [14C]PAH concentration increased to about the same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na+-dicarboxylate cotransport) in bathing medium during α-KG preloading eliminated stimulation of PAH transport. Addition of unlabeled α-KG (1 mM) to bathing medium stimulated efflux of [14C]PAH across the basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH/ α-KG countertransport. Preloading with succinate (100 μM) also stimulated rates of [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only ∼1.5-fold. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate [14C]PAH uptake by nonperfused tubules or net secretion by perfused tubules. Thus it seems most likely that succinate preloading stimulates PAH transport via metabolism, possibly by conversion to α-KG, not by direct countertransport for PAH. This study indicates for the first time in intact mammalian proximal S2 renal tubules that PAH/α-KG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.

AB - Possible stimulation of both basolateral uptake and net transepithelial secretion of p-aminohippurate (PAH) by PAH/α-ketoglutarate (α-KG) countertransport was examined in intact perfused and nonperfused rabbit proximal S2 renal tubules. Preloading tubules with α-KG (100 μM) for 30 min increased [14C]-PAH rate of uptake by nonperfused tubules and rate of net secretion by perfused tubules approximately three- to sixfold. During stimulation of net secretion, intracellular [14C]PAH concentration increased to about the same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na+-dicarboxylate cotransport) in bathing medium during α-KG preloading eliminated stimulation of PAH transport. Addition of unlabeled α-KG (1 mM) to bathing medium stimulated efflux of [14C]PAH across the basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH/ α-KG countertransport. Preloading with succinate (100 μM) also stimulated rates of [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only ∼1.5-fold. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate [14C]PAH uptake by nonperfused tubules or net secretion by perfused tubules. Thus it seems most likely that succinate preloading stimulates PAH transport via metabolism, possibly by conversion to α-KG, not by direct countertransport for PAH. This study indicates for the first time in intact mammalian proximal S2 renal tubules that PAH/α-KG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.

KW - Dicarboxylate/organic anion countertransport

KW - Organic anion transport

KW - Succinate

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