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Renal contraluminal transport systems for organic anions (paraaminohippurate, PAH) and organic cations (N1 methyl-nicotinamide, NMeN) do not see the degree of substrate ionization

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  • Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands
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Abstract

Using the stop-flow peritubular capillary microperfusion method pH dependence of the interaction of different substrates with the contraluminal PAH- and NMeN transporter was investigated. Substrates for both transport systems with pKa values around 7.0 were chosen and the pH of the perfusates was varied between 6.0 and 8.0. The inhibitory potencies (app. Ki values) were determined and the influx into the proximal tubular cells was measured. The app. Ki(NMeN) values of imidazole (pKa 7.03), a substrate for the NMeN-transporter, the app. KiPAH values of the dipeptide tryptophyl-tryptophan (pKa 7.36), a'substrate for the PAH-transporter, and the app. Ki,NMeN and Ki,PAH of cimetidine (pKa 6.98) and buspirone (pKa 7.2) which interact with both transport systems, did not vary between perfusate pH 6.0 and 8.0. The same holds for the influx of 3H-cimetidine into proximal tubular cells. The data indicate that both transporters have no preference for the ionized form of their substrates and that the name organic anion and organic cation transporter resides rather on history than on molecular interaction.

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Ullrich, K.J., Rumrich, G. Renal contraluminal transport systems for organic anions (paraaminohippurate, PAH) and organic cations (N1 methyl-nicotinamide, NMeN) do not see the degree of substrate ionization. Pflügers Arch 421, 286–288 (1992). https://doi.org/10.1007/BF00374841

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  • DOI: https://doi.org/10.1007/BF00374841

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