Organic cation transport in avian renal brush-border membrane vesicles.
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Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.Abstract
The objective of this study was to characterize the transport of organic cations (OCs) at the luminal brush-border membrane of the avian renal proximal tubule. Using membrane vesicles isolated from renal tissue of chickens (Gallus domesticus), transport of the exogenous OC[¹⁴C]tetraethylammonium (TEA) was measured by rapid filtration under various ionic conditions. A trans proton gradient stimulated concentrative uptake of TEA. Tetraethylammonium/proton exchange was a saturable, qualitatively symmetrical process that was indirectly coupled to Na⁺/H⁺ antiport. Proton-driven uptake of TEA was not electrogenic; however, it was sensitive to changes in transmembrane potential. Proton-driven TEA uptake was apparently selectively inhibited by OCs. To evaluate substrate specificity of OC/H⁺ exchanger, a battery of endogenous and exogenous OCs were tested for cis inhibition and trans stimulation of [¹⁴C]TEA transport. Although amiloride, cimetidine, mepiperphenidol, procainamide, quinidine, quinine, ranitidine and thiamine were potent cis inhibitors of TEA transport, they were poorly transported by the exchanger. Conversely, acetylcholine, choline, epinephrine, guanidine, isoproterenol, N¹methylnicotinamide, serotonin, and unlabeled TEA, modestly inhibited TEA transport, but trans stimulated transport. Inhibitor-induced changes in the kinetic parameters of TEA/H⁺ exchange suggested serotonin and thiamine competed with TEA for the substrate site on the exchanger, whereas inhibition by amiloride, procainamide, and quinidine apparently involved binding to allosteric sites on the carrier. These data suggest luminal transport of OCs in the avian proximal tubule is qualitatively similar to that in mammals. Moreover, the OC/H⁺ exchanger of avian BBMV has greater affinity for exogenous compounds than for endogenous compounds; however, it has a greater capacity to transport endogenous OCs than exogenous OCs.Type
textDissertation-Reproduction (electronic)
Degree Name
Ph.D.Degree Level
doctoralDegree Program
PhysiologyGraduate College