A comparative study on the accumulation of probenecid and analogues in rabbit kidney tubules in vitro

The characteristics of renal accumulation of probenecid (di-n-propylsulfamylbenzoic acid) and di-methyl CH₃]₂R,di-ethyl C₂H₅]₂R, and di-butyl C₄H₉]₂R analogues by cortical slices suspended in an electrolyte medium have been compared. The compounds were accumulated both under aerobic and anaerobic conditions. Rate of initial active uptake increased in the order: CH₃]₂R < C₂H₅]₂R = C₃H₇]₂R > C₄H₉]₂-R. The compounds inhibited the aerobic uptake of PAH and phenol red with the following order of effectiveness: CH₃]₂R < C₂H₅]₂R < C₃H₇]₂R < C₄H₉]₂R. PAH affected the accumulation of probenecid and analogues in the reverse order. The accumulation of probenecid and analogues under anaerobic conditions could be accounted for by binding to various tissue constituents and exhibited close similarity to binding to human serum albumin and liposomes. Phenol red, in contrast to PAH, inhibited anaerobic binding of the compounds to various extents. Active accumulation of probenecid and analogues was markedly stimulated by acetate (10 mM), while fumarate and octanoate had a biphasic effect, except on the accumulation of dibutyl analogue which was little influenced by these metabolites. It is concluded that probenecid and analogues are actively transported by the organic anion system. The inhibitory potency is correlated with the hydrophobicity of these compounds as in the case of phenolsulphonphthalein dyes.