Coupled transport of p-aminohippurate by rat kidney basolateral membrane vesicles.
p-Aminohippuric acid (PAH) transport by basolateral membrane (BLM) vesicles isolated from rat renal cortex was stimulated very little by a Na+ gradient (out greater than in). However, when micromolar concentrations of glutaric acid or alpha-ketoglutaric acid were added in the presence of a out greater than in Na+ gradient, PAH uptake was accelerated greater than 20-fold and an overshoot of greater than fivefold was produced. Other anions, e.g., fumarate, stimulated PAH uptake very modestly under these conditions (approximately 2-fold), and that stimulation was totally prevented by short circuiting, i.e., with K+ (in = out) and valinomycin. Glutarate-stimulated uptake was inhibited by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) and probenecid and was slightly stimulated by the imposition of an inside-negative membrane potential. Furthermore, even in the absence of a Na+ gradient, glutarate-loaded vesicles exhibited a marked acceleration of PAH uptake (5-fold) and a modest overshoot (2.5-fold). These results suggest an indirect coupling of BLM PAH uptake to the Na+ gradient by a cyclic accumulation (Na+-dependent) of glutarate followed by its efflux from the vesicle in exchange for PAH. This coupled system was absent in apical membranes. Thus net secretory transport of PAH may entail Na+-dependent, glutarate-driven PAH uptake at the BLM, followed by the exit of PAH into the lumen down its electrochemical gradient, probably in exchange for other anions, e.g., Cl-, HCO3-, or OH-.
Pritchard
J B
JB
Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D000838:Anions; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D005977:Glutarates / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D051381:Rats; D011916:Rats, Inbred F344; D010130:p-Aminohippuric Acid / Q000378:metabolism* / Q000494:pharmacology
D000618:Aminohippuric Acids; D000838:Anions; D005977:Glutarates; D008094:Lithium; D010130:p-Aminohippuric Acid