Characterization of organic cation transport by avian renal brush-border membrane vesicles

Abstract

Organic cations are actively secreted by the renal proximal tubule. Studies on perfused tubules and isolated membranes from mammals and reptiles have demonstrated that organic cations (OC) are transported across the luminal (brush-border) membrane by OC/H+ exchange. Our objective was to determine whether a similar mechanism was present in the avian kidney. Uptake of [14C]tetraethylammonium (TEA) was assayed under various ionic conditions by rapid filtration in brush-border membrane vesicles (BBMV) isolated from chicken kidney (Gallus domesticus). An outwardly directed proton gradient (pHin = 6.0: pHout = 7.5) stimulated concentrative TEA uptake. TEA/H+ exchange was saturable, having a maximal rate of uptake of approximately 25 nmol.mg protein-1.min-1 and a Michaelis constant for TEA of approximately 500 microM. TEA transport could be indirectly coupled to sodium transport. Unlabeled TEA, N'-methylnicotinamide (NMN), choline, cimetidine, mepiperphenidol, quinidine, quinine, and ranitidine markedly cis-inhibited uptake of [14C]TEA. However, the organic anions probenecid and p-aminohippurate poorly inhibited uptake. Unlabeled TEA and NMN also trans-stimulated [14C]TEA uptake. Thus, in avian renal BBMV, organic cations are transported by an OC/H+ exchange mechanism qualitatively similar to that present in mammals.