INHIBITION OF THE RENAL TUBULAR TRANSPORT AND EXCRETION OF TETRAETHYLAMMONIUM AND N¹-METHYLNICOTINAMIDE BY NON-NITROGENOUS ONIUM COMPOUNDS

¹ Department of Pharmacology, University of Kansas Medical Center, Kansas City, Kansas

A renal tubular transport system which mediates excretion of amines and quaternary ammonium compounds exists in mammals and birds. The many types of compounds transported by this system, or inhibiting it competitively, suggest the major requirement for their interaction with the system to be a cationic nitrogen. To characterize this renal tubular transport system further, in the presence of varying concentrations of several non-nitrogenous enous onium compounds, the accumulation of tetraethylammonium (TEA) by slices of chicken kidney, the accumulations of N¹-methylnicotiamide (NMN) by slices of dog kidney and the renal tubular excretion of NMN in the hen were examined. Onium derivatives of P, As, Sb and S, in concentrations not affecting oxygen consumption or p-aminohippuric acid renal transport, inhibited the uptake of TEA and NMN by renal slices and the renal tubular excretion of NMN by the hen. The results are interpreted as indicating an anionic site on the receptor or carrier in the renal tubular cell which is responsible for mediating the renal tubular excretory transport of organic cations, i.e., a cellular anionic site which reacts with the cationic head of compounds transported by or capable of competitively inhibiting the system.