THE REVERSIBLE AND IRREVERSIBLE INHIBITION OF N¹-METHYLNICOTINAMIDE UPTAKE INTO RAT KIDNEY CORTEX SLICES

¹ Department of Pharmacology, State University of New York School of Medicine, Buffalo, New York

The uptake of N¹-methyinicotinamide (NMN) and p-aminohippuric acid by rat kidney cortex slices was measured. Measurement of inhibition of NMN uptake by various NMN analogs has shown that inhibition is not favored at any particular position on the ring. Inhibition by a series of N¹-alkylnicotinamides demonstrated an increasing interaction between inhibitor and transport system as the alkyl chain was increased from two to six carbons with no further increase in interaction past six carbons. The partition of the N¹-alkylnicotinamides between 1-octanol and water is reported, and the possible hydrophobic interaction between these compounds and the transport system is discussed. The conclusions based on the N¹- alkylnicotinamide experiments are substantiated by use of a series of irreversible inbibitions, 2-haloethylamines. The use of the information in the design of further irreversible inhibitors and the application of these inhibitors in the isolation of the membrane proteins involved in uptake of NMN are discussed.

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