Coordinate regulation of systemic and kidney tryptophan metabolism by the drug transporters OAT1 and OAT3.

ABSTRACT: How organs sense circulating metabolites is a key question. Here, we show that the multispecific organic anion transporters of drugs, OAT1 (SLC22A6 or NKT) and OAT3 (SLC22A8), play a role in organ sensing. Metabolomics analyses of the serum of Oat1 and Oat3 knockout mice revealed changes in tryptophan derivatives involved in metabolism and signaling. Several of these metabolites are derived from the gut microbiome and are implicated as uremic toxins in chronic kidney disease. Direct interaction with the transporters was supported with cell-based transport assays. To assess the impact of the loss of OAT1 or OAT3 function on the kidney, an organ where these uptake transporters are highly expressed, knockout transcriptomic data were mapped onto a "metabolic task"-based computational model tha

SUBMITTER: Granados JC 

PROVIDER: S-EPMC8102410 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature