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

Varanuj Chatsudthipong, William H Dantzler

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31 Citations (Scopus)

Abstract

The possibility that p-aminohippurate (PAH)-α-ketoglutarate (αKG) countertransport could stimulate basolateral uptake and net transepithelial secretion of PAH was examined in intact isolated nonperfused and perfused snake (Thamnophis spp.) distal proximal 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 fivefold without increasing cellular ATP content. During stimulation of net secretion, intracellular [14C]PAH concentration increased to same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na+-dicarboxylate cotransport) in bath during αKG preloading eliminated stimulation of PAH transport. Addition of unlabeled α-KG to bathing medium stimulated efflux of [14C]PAH across basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH-α-KG countertransport. Preloading with succinate (100 μM) also stimulated [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only 1.5- to 2-fold and cellular ATP content increased. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate PAH uptake by nonperfused tubules or secretion by perfused tubules. Thus succinate appears to stimulate PAH transport via metabolism, possibly by conversion to α-KG, not by direct countertransport. This study indicates for the first time in intact renal tubules that PAH-αKG 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
Volume261
Issue number5 30-5
StatePublished - 1991

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p-Aminohippuric Acid
Snakes
Kidney
Succinic Acid
Adenosine Triphosphate
Distal Kidney Tubule
Colubridae
Proximal Kidney Tubule
Baths

Keywords

  • Cellular adenosine 5′-triphosphate
  • Dicarboxylate-organic anion countertransport
  • Garter snakes
  • Organic anion transport
  • Succinate
  • Thamnophis

ASJC Scopus subject areas

  • Physiology

Cite this

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abstract = "The possibility that p-aminohippurate (PAH)-α-ketoglutarate (αKG) countertransport could stimulate basolateral uptake and net transepithelial secretion of PAH was examined in intact isolated nonperfused and perfused snake (Thamnophis spp.) distal proximal 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 fivefold without increasing cellular ATP content. During stimulation of net secretion, intracellular [14C]PAH concentration increased to same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na+-dicarboxylate cotransport) in bath during αKG preloading eliminated stimulation of PAH transport. Addition of unlabeled α-KG to bathing medium stimulated efflux of [14C]PAH across basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH-α-KG countertransport. Preloading with succinate (100 μM) also stimulated [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only 1.5- to 2-fold and cellular ATP content increased. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate PAH uptake by nonperfused tubules or secretion by perfused tubules. Thus succinate appears to stimulate PAH transport via metabolism, possibly by conversion to α-KG, not by direct countertransport. This study indicates for the first time in intact renal tubules that PAH-αKG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.",
keywords = "Cellular adenosine 5′-triphosphate, Dicarboxylate-organic anion countertransport, Garter snakes, Organic anion transport, Succinate, Thamnophis",
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journal = "American Journal of Physiology",
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T1 - PAH-α-KG countertransport stimulates PAH uptake and net secretion in isolated snake renal tubules

AU - Chatsudthipong, Varanuj

AU - Dantzler, William H

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N2 - The possibility that p-aminohippurate (PAH)-α-ketoglutarate (αKG) countertransport could stimulate basolateral uptake and net transepithelial secretion of PAH was examined in intact isolated nonperfused and perfused snake (Thamnophis spp.) distal proximal 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 fivefold without increasing cellular ATP content. During stimulation of net secretion, intracellular [14C]PAH concentration increased to same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na+-dicarboxylate cotransport) in bath during αKG preloading eliminated stimulation of PAH transport. Addition of unlabeled α-KG to bathing medium stimulated efflux of [14C]PAH across basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH-α-KG countertransport. Preloading with succinate (100 μM) also stimulated [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only 1.5- to 2-fold and cellular ATP content increased. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate PAH uptake by nonperfused tubules or secretion by perfused tubules. Thus succinate appears to stimulate PAH transport via metabolism, possibly by conversion to α-KG, not by direct countertransport. This study indicates for the first time in intact renal tubules that PAH-αKG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.

AB - The possibility that p-aminohippurate (PAH)-α-ketoglutarate (αKG) countertransport could stimulate basolateral uptake and net transepithelial secretion of PAH was examined in intact isolated nonperfused and perfused snake (Thamnophis spp.) distal proximal 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 fivefold without increasing cellular ATP content. During stimulation of net secretion, intracellular [14C]PAH concentration increased to same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na+-dicarboxylate cotransport) in bath during αKG preloading eliminated stimulation of PAH transport. Addition of unlabeled α-KG to bathing medium stimulated efflux of [14C]PAH across basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH-α-KG countertransport. Preloading with succinate (100 μM) also stimulated [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only 1.5- to 2-fold and cellular ATP content increased. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate PAH uptake by nonperfused tubules or secretion by perfused tubules. Thus succinate appears to stimulate PAH transport via metabolism, possibly by conversion to α-KG, not by direct countertransport. This study indicates for the first time in intact renal tubules that PAH-αKG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.

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KW - Dicarboxylate-organic anion countertransport

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