Metabolism of salicylic acid in the isolated perfused rat kidney. Interconversion of salicyluric and salicyclic acids.
Renal metabolism of salicylic acid (SA) to salicyluric acid (SU), as well as the metabolism of SU to SA, was demonstrated in the isolated perfused rat kidney. SU formation was dependent upon the inclusion of a glycine pool and glycine concentration influenced the rate of SU excretion. The total conversion of SA to SU in 1 hr was 7.7% after the administration of 1 mg SA. Administration of increasing amounts of SA diminished this extent of SU formation. The addition of a competitive substrate, benzoic acid, produced a rapid formation and excretion of hippuric acid with a corresponding inhibition of SU formation and excretion. It is important to note that when isolated kidneys were perfused with 2.5 mg SU, 20--30% of the dose was metabolized to SA. Increasing the dose of SU to 10 mg decreased the amount of SA formed. In view of observed reversible SA/SU metabolism, a larger renal contribution to overall salicylate disposition is suggested.
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D006626:Hippurates / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D012459:Salicylates / Q000378:metabolism*
D001565:Benzoates; D006626:Hippurates; D012459:Salicylates; C000693:salicylurate; D005998:Glycine