p-Aminohippurate transport in airways: competitive inhibition.
p-Aminohippurate (PAH) transport in canine tracheal epithelium occurs by a HCO3- -PAH exchange process that is located on the luminal membrane and is inhibited by stilbene derivatives. The effects of increasing concentrations of other organic anions, including probenecid (10-250 microM), dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP; 10-1,000 microM), phenol red (10-250 microM), and urate (25-500 microM), and the organic cation tetraethylammonium bromide (TEA; 250 microM) on PAH transport were examined in canine tracheal epithelium mounted in Ussing chambers. Neither phenol red, urate, nor TEA had any effect on electrophysiological properties or unidirectional or net PAH fluxes. In contrast, beginning at 10 microM, both probenecid and cAMP produced significant decreases in unidirectional and net PAH absorption without change in unidirectional PAH secretion. The initial change in net PAH absorption occurred in the absence of any change in electrophysiological properties. Higher concentrations of both probenecid and cAMP produced further decreases in net PAH absorption and significant changes in electrophysiological properties. Probenecid and cAMP increased the apparent Michaelis constant for PAH absorption without affecting maximum transport rate. The inhibitory constant for probenecid was 1.01 +/- 0.06 x 10(-4) M (mean +/- SE) and for cAMP was 5.18 +/- 0.20 x 10(-4) M. We conclude that PAH transport in canine tracheal epithelium demonstrates competitive inhibition by other organic anions and substrate specificity. We also conclude that the affinity of the exchange transport system is higher for probenecid than for PAH and cAMP.
Cloutier
M M
MM
Department of Pediatrics, University of Connecticut Health Center, Farmington 06030.
Guernsey
L
L
D000818:Animals; D001692:Biological Transport; D000242:Cyclic AMP / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D010637:Phenolsulfonphthalein / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism* / Q000502:physiology; D014527:Uric Acid / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*
D014527:Uric Acid; D000242:Cyclic AMP; D010637:Phenolsulfonphthalein; D011339:Probenecid; D010130:p-Aminohippuric Acid