Molecular features of sulfonamide transport in renal excretory processes

Abstract

Renal tubular excretory transport of selected sulfonamides is assumed to require a physicochemical interaction between the substrate and a postulated intracellular receptor molecule. It is proposed that substrate specificity in this transport system depends on the presence of the intramolecular sequence, (See PDF for Equation), in the sulfonamide. Reactivity of this group requires ionization at N, localization of the net negative charge at N, and electronegativity at each oxygen sufficient for the formation of hydrogen bonds. Presence of these three features in favorable combination permits transport. A three-point contact with the receptor can be described involving the anionic locus and both oxygens of the substrate. These proposals are supported by analysis of the physicochemical, biochemical, and physiological behavior of 52 sulfonamides both in surviving rabbit renal cortical slices (original observations) and in intact mongrel dogs (survey of representative published reports). Although transport of sulfonamides is treated as an independent biochemical mechanism, its relation to the renal hippurate transport system is recognized and similar responses of both classes of substrates to probenecid or to acetate are demonstrated experimentally.