ACCUMULATION OF CIMETIDINE BY KIDNEY CORTEX SLICES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 221  (2) , 342-346
Abstract
The mechanisms involved in the excretion of the histamine H2-receptor antagonist cimetidine [used to inhibit gastric acid secretion] are as yet incompletely understood. The interaction of cimetidine with incubated slices of dog kidney cortex was studied. The results of time and concentration-dependent experiments by using 3H-labeled cimetidine demonstrated that the drug was accumulated without metabolism against a concentration gradient by a saturable process. Inhibition of uptake by cyanide and by incubation under a N atmosphere indicated energy dependence. Uptake of cimetidine by active cationic transport was likely inasmuch as both cyanine 863 and quinine blocked accumulation. A probenecid-sensitive component, accounting for .apprx. 20% of steady-state accumulation, also was identified. The lack of inhibitory action of p-aminohippuric acid and the cationic nature of the cimetidine molecule suggest the probenecid-sensitivity was not related to the renal organic anion mechanism. Probenecid inhibition was not due to a generalized cellular toxicity because maximally inhibitory concentrations of probenecid did not interfere with uptake of the cation tetraethylammonium.