Abstract The aryl hydrocarbon receptor (AHR) is a transcription factor with roles in detoxification, development, immune response, chronic kidney disease and other syndromes. It regulates the expression of drug transporters metabolizing enzymes proposed Remote Sensing Signaling Network involved inter-organ communication via metabolites signaling molecules. Here, we use integrated omics approaches to analyze its contributions metabolism across multiple scales from organ organelle. Global...

The SLC22 family of OATs, OCTs, and OCTNs is emerging as a central hub endogenous physiology. Despite often being referred to "drug" transporters, they facilitate the movement metabolites key signaling molecules. An in-depth reanalysis supports reassignment these proteins into eight functional subgroups, with four new subgroups arising from previously defined OAT subclade: OATS1 (SLC22A6, SLC22A8, SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, Slc22a22), OATS4 (SLC22A9, SLC22A10,...

Probenecid is used to treat gout and hyperuricemia as well increase plasma levels of antiviral drugs antibiotics. In vivo, probenecid mainly inhibits the renal SLC22 organic anion transporters OAT1 (SLC22A6), OAT3 (SLC22A8), URAT1 (SLC22A12). To understand endogenous role these in humans, we administered 20 healthy participants metabolically profiled urine before after dosage. Hundreds metabolites were significantly altered, indicating numerous drug-metabolite interactions. We focused on...

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 role in organ sensing. Metabolomics analyses serum Oat1 Oat3 knockout mice revealed changes tryptophan derivatives involved metabolism signaling. Several these are derived from gut microbiome implicated as uremic toxins chronic kidney disease. Direct interaction with was supported cell-based transport assays. To...

Multislice maps of extracellular pH (pHe) are needed to interrogate the heterogeneities tumors and normal organs. To address this need, we have developed a multislice chemical exchange saturation transfer (CEST) MRI acquisition method with CEST spectrum-fitting that measures in vivo pHe over range 6.3 7.4.The phase offset multiplanar (POMP) was adapted for fast imaging steady-state free precession (FISP) acquire multiple image slices single pulse. The Bloch-McConnell equations were modified...

Organic anion transporter 1 (OAT1/SLC22A6) is a drug with numerous xenobiotic and endogenous substrates. The Remote Sensing Signaling Theory suggests that transporters compatible ligand preferences can play role in "organ crosstalk," mediating overall organismal communication. Other are well known to transport lipids, but surprisingly little about the of OAT1 lipid metabolism. To explore this subject, we constructed genome-scale metabolic model using omics data from Oat1 knockout mouse....

Organic anion transporter 1 (OAT1/SLC22A6, NKT) is a multispecific drug in the kidney with numerous substrates, including pharmaceuticals, endogenous metabolites, natural products, and uremic toxins. Here, we show that OAT1 regulates levels of gut microbiome-derived metabolites. We depleted microbiome Oat1-KO WT mice performed metabolomics to analyze effects genotype (KO versus WT) depletion. an vivo intermediary between host microbes, 40 162 metabolites dependent on also impacted by loss...

The organic anion transporters OAT1 (SLC22A6) and OAT3 (SLC22A8) are drug that expressed in the kidney, with well-established roles vivo transport of drugs endogenous metabolites. A comparatively unexplored potential function these is their contribution to regulation natural products (NPs) effects on metabolism. This important for evaluation NP interactions other compounds at transporter site. Here, we have analyzed NPs present several databases from Asian (Chinese, Indian Ayurvedic)...

The SLC22 family of transporters is widely expressed, evolutionarily conserved, and plays a major role in regulating homeostasis by transporting small organic molecules such as metabolites, signaling molecules, antioxidants. Analysis fruit flies provides simple yet orthologous platform to study the endogenous function drug vivo. Evolutionary analysis Drosophila melanogaster putative orthologs reveals that, while many 25 fly do not fall within previously established subclades, at least four...

The organic anion transporter OAT1 (SLC22A6, originally identified as NKT) is a multispecific responsible for the elimination by kidney of small anions that derive from gut microbiome. Many are uremic toxins associated with chronic disease (CKD). among group "drug" transporters act hubs in large homeostatic network regulating interorgan and interorganismal communication via molecules. Remote Sensing Signaling Theory predicts genetic deletion such key hub results compensatory (e.g., host-gut...

Drug transporters and drug-metabolizing enzymes are primarily known for their role in the absorption, distribution, metabolism, excretion (ADME) of small molecule drugs, but they also play a key handling endogenous metabolites. Recent cross-tissue co-expression network analyses have revealed "Remote Sensing Signaling Network" multispecific, oligo-specific, monospecific involved metabolism. This includes many proteins from families ADME (e.g., SLC22, SLCO, ABCC, CYP, UGT). Focusing on...

Abstract Among transporters, the SLC22 family is emerging as a central hub of endogenous physiology. The consists organic anion transporters (OATs), cation (OCTs) and zwitterion (OCTNs). Despite being known “drug” these multi-specific, oligo-specific, relatively mono-specific facilitate movement metabolites key signaling molecules. An in-depth reanalysis supports reassignment proteins into eight functional subgroups with four new arising from previously defined OAT subclade. These are: OATS1...