Voltage-driven p-aminohippurate, chloride, and urate transport in porcine renal brush-border membrane vesicles.
p-Aminohippurate (PAH) and urate are secreted into the proximal tubule lumen across the brush-border membrane. Here we used brush-border membrane vesicles from pig kidney to study PAH and urate transport. Efflux and influx of [3H]PAH were influenced by K+-diffusion potentials indicating electrogenic PAH transport. An outside>inside PAH concentration difference accelerated voltage-sensitive, Na+-coupled D-glucose uptake as efficiently as did an outside>inside Cl- concentration difference, suggesting comparable conductances for PAH and Cl- in brush-border membrane vesicles. Up to 1 mM of the uricosurics indacrinone, tienilic acid, losartan and probenecid, as well as of the stilbenes, DIDS and SITS, and of the loop diuretics furosemide and bumetanide inhibited voltage-driven PAH uptake, but not, or only slightly, voltage-driven Cl- uptake. Voltage-driven [14C]urate uptake, however, was inhibited by 0.1 mM DIDS, 0.2 mM losartan and 0.5 mM probenecid to a similar extent as [3H]PAH uptake. One millimolar pyrazinoic acid, oxonate, xanthine and adenosine inhibited neither [3H]PAH nor [14C]urate uptake. These results suggest that PAH and urate share an anion conductance which is distinct from the Cl- conductance and is probably not the same as a recently identified urate channel (Leal-Pinto E et a]. J Biol Chem 272:617-625, 1997).
Krick
W
W
Abteilung Vegetative Physiologie und Pathophysiologie, Zentrum Physiologie und Pathophysiologie, Göttingen, Germany. Krick@veg-physiol.med.uni-goettingen.de
Wolff
N A
NA
Burckhardt
G
G
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism*; D004058:Diffusion; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D007668:Kidney / Q000648:ultrastructure*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008564:Membrane Potentials; D008871:Microvilli / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013552:Swine; D014316:Tritium; D014527:Uric Acid / Q000378:metabolism*; D014634:Valinomycin / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000378:metabolism
D002712:Chlorides; D004232:Diuretics; D007476:Ionophores; D002034:Bumetanide; D014316:Tritium; D014634:Valinomycin; D014527:Uric Acid; D005665:Furosemide; D012964:Sodium; D005947:Glucose; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium; D010130:p-Aminohippuric Acid