PAH/alpha-KG countertransport stimulates PAH uptake and net secretion in isolated rabbit renal tubules.
Possible stimulation of both basolateral uptake and net transepithelial secretion of p-aminohippurate (PAH) by PAH/alpha-ketoglutarate (alpha-KG) countertransport was examined in intact perfused and nonperfused rabbit proximal S2 renal tubules. Preloading tubules with alpha-KG (100 microM) 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 alpha-KG preloading eliminated stimulation of PAH transport. Addition of unlabeled alpha-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/alpha-KG countertransport. Preloading with succinate (100 microM) also stimulated rates of [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only approximately 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 alpha-KG, not by direct countertransport for PAH. This study indicates for the first time in intact mammalian proximal S2 renal tubules that PAH/alpha-KG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.
Chatsudthipong
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Department of Physiology, University of Arizona, College of Medicine, Tucson 85724.
Dantzler
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WH
D000818:Animals; D000838:Anions / Q000494:pharmacology; D001693:Biological Transport, Active; D003998:Dicarboxylic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007656:Ketoglutaric Acids / Q000378:metabolism* / Q000494:pharmacology; D007684:Kidney Tubules / Q000378:metabolism*; D011817:Rabbits; D013386:Succinates / Q000494:pharmacology; D019802:Succinic Acid; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000838:Anions; D003998:Dicarboxylic Acids; D007656:Ketoglutaric Acids; D013386:Succinates; D019802:Succinic Acid; D010130:p-Aminohippuric Acid