TY - JOUR T1 - Renal N-oxidation of trimethylamine in the chicken during tubular excretion. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 82 LP - 90 VL - 5 IS - 1 AU - M Acara AU - S Camiolo AU - B Rennick Y1 - 1977/01/01 UR - http://dmd.aspetjournals.org/content/5/1/82.abstract N2 - The Sperber technique of infusion into the renal portal circulation in chickens was used to investigate in vivo the renal tubular transport and renal metabolism of trimethylamine (TMA). When 14C-TMA was infused at a rate of 1 x 10(-9) mol/min the transport efficiency (TE), that is, the tubular excretion of the 14C-label relative to excretion of simultaneously infused paminohippuric acid, was 0.70. Progressive addition of unlabeled TMA up to infusion rates of 1 x 10(-5) mol/min produced a progressive fall in the TE of the 14C-label. Identification of the 14C-label excreted in the urine revealed that approximately 85% of the infused 14C-TMA was excreted by the infused kidney as a single metabolite over the entire range of infusions. By use of the techniques of low-voltage electrophoresis, high-voltage electrophoretic mobility-pH profile, and gas chromatography/mass spectrometry, the renal metabolite was found to be identical with standard 14C-trimethylamine oxide (TMAO). At a TMA infusion rate of 1.5 x 10(-6) mol/kg/min reaching the infused kidney, the rate at which TMAO was formed and excreted by the kidney was 0.12 x 10(-6) mol per g of kidney per min. When 14C-TMAO was infused into chickens its TE was 0.11, which was not evidence for active excretory transport. Infused TMA was almost entirely metabolized in vivo to its N-oxide, TMAO, which then entered the urine. The renal tubular excretion of 14C during infusion of 14C-TMA was inhibited by the cationic blocker of transport, quinine, and by the anionic blocker of transport, probenecid. ER -