Ask about this productRelated genes to: SLC22A6 Blocking Peptide
- Gene:
- SLC22A6 NIH gene
- Name:
- solute carrier family 22 member 6
- Previous symbol:
- -
- Synonyms:
- ROAT1, PAHT, OAT1
- Chromosome:
- 11q12.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-30
- Date modifiied:
- 2016-02-17
Related products to: SLC22A6 Blocking Peptide
Related articles to: SLC22A6 Blocking Peptide
- Organic anion transporters (OATs, SLC22) in the kidney and organic anion-transporting polypeptides (OATPs, SLCO) in the liver play crucial roles in the disposition of small molecule drugs that are organic anions. According to the Remote Sensing and Signaling Theory, these multispecific "drug" transporters are also central to crosstalk between the liver, kidney, and other organs via endogenous small molecules (e.g., metabolites, signaling molecules, gut microbiome products). These multispecific drug transporters govern access of small molecules with high informational content across multiple scales (organism to organelle). Previous chemoinformatic and machine learning methods have proven useful for identifying molecular properties of organic anion drugs that predispose them to handling by the OAT (renal) and the OATP (hepatic) transporters. This is important for understanding pharmacokinetics (ADME) in the context of chronic kidney disease (CKD) and liver disease. Given that OATs and OATPs are involved in many metabolic diseases, we sought to determine whether molecular properties could be identified for distinguishing OAT- versus OATP-interacting endogenous metabolites . This is essential for understanding endogenous small molecule communication between the kidney proximal tubule and hepatocytes in a larger Remote Sensing and Signaling System. We analyzed metabolomics data from OAT and OATP knockout mice, focusing on endogenous metabolites selective for OATs (e.g., OAT1 or SLC22A6; OAT3 or SLC22A8) vs OATPs (including the locus containing Oatp1b2, the closest homologue of human OATP1B1 or SLCO1B1 and OATP1B3 or SLCO1B3). Applying chemoinformatic methods to a data set of 210 metabolites based on knockout mouse metabolomics (92 OAT-selective, 118 OATP-selective), we identified a set of distinguishing molecular properties (e.g., MolLogP, RingCount, NumRotatableBonds). We then used machine learning approaches (e.g., Random Forest, Naive Bayes, Logistic Regression) to classify OAT vs OATP metabolites, achieving over 75% accuracy. These results support the view that transporter knockout mouse metabolomics can help define selectivity of SLC drug transporters for endogenous metabolites, signaling molecules, antioxidants, nutrients, and gut microbiome products. In the context of the Remote Sensing and Signaling Theory, we discuss the implications for understanding organ crosstalk and interorganismal communication as well as drug disposition, drug-metabolite interactions, and metabolite-based drug design. - Source: PubMed
Publication date: 2026/04/16
Nigam Anisha KFalah KianMomper Jeremiah DNigam Sanjay K - Citrate plays a crucial role in preventing calcium stone formation by chelating calcium and inhibiting crystal aggregation. Organic anion transporters (OATs), expressed in renal proximal tubules, mediate the transport of various organic anions, including drugs. However, whether OATs transport citrate and oxalate-key metabolites involved in urinary stone formation-remains unclear. This study aimed to determine whether OATs contribute to citrate and oxalate transport and to clarify their underlying mechanisms. Uptake experiments were conducted using S2 cells stably expressing human OAT1, OAT3, or OAT4. Substrate uptake was measured using radiolabeled compounds, and [C]citrate uptake was evaluated for time and concentration dependence, and inhibition by various compounds. OAT4, localized to the apical membrane, exhibited significantly increased [C]citrate uptake under acidic conditions (pH 6.0), whereas OAT1 and OAT3 showed minimal pH dependence. OAT4-mediated citrate uptake increased in a time-dependent manner and showed biphasic kinetics. Citrate transport was unaffected by endogenous dicarboxylates but inhibited by diuretics and nonsteroidal anti-inflammatory drugs. These findings identify OAT4 as a novel citrate transporter. Enhanced OAT4 activity under acidic conditions may promote citrate reabsorption, thereby increasing the risk of calcium stone formation. Targeting OAT4 with specific inhibitors could represent a new therapeutic strategy for preventing urinary stone recurrence. - Source: PubMed
Publication date: 2026/02/18
Ikematsu YukiPengrattanachot NattavadeeReien YoshieSeito JunSaito ShotaHirayama YuriOuchi MotoshiSakamoto ShinichiHashimoto HirofumiAnzai Naohiko - Ochratoxin C (OTC) is a commonly overlooked toxin in the ochratoxin family, found in moldy crops and poultry meat. However, its potential toxicity should not be ignored and needs further elucidation. In this study, we evaluated the neurotoxicity of OTC during zebrafish embryonic development. The results show that OTC affects the overall zebrafish embryonic development, resulting in reduced body length, abnormal hatching, increased yolk sac area, and decreased tail flick frequency. Additionally, OTC specifically induces cerebral hemorrhaging and abnormal motor behavior in these embryos, accompanied by changes in neurotransmitter and neurodevelopment-related gene expression levels. Furthermore, OTC induces upregulation of oxidative stress levels and downregulation of acetylcholinesterase (AChE) activity and adenosine triphosphatase (ATPase) activity, leading to cell apoptosis.Transcriptional assays and transgenic fluorescence photography show that OTC can inhibit Notch signaling pathway. Partial restoration of cerebral hemorrhage and neurodevelopmental defects can be achieved by administering the Notch signaling activator, sodium propionate. Molecular docking analysis indicates that the gene SLC22A6 (corresponding to the human gene OAT1) as the binding target protein for OTC. In conclusion, OTC exposure may lead to zebrafish embryonic neurodevelopmental defects and cerebral hemorrhage by downregulating Notch signaling. This work provides insight into the potential threat of OTC to embryonic development. - Source: PubMed
Publication date: 2025/06/06
Hu BoxiYang DouYuan QiangWang ZhipengLiu JiejunXu JialiLiu FashengZhang ShouhuaLiao XinjunXiao JuhuaCao Zigang - Ampicillin (AMP) is an organic anion drug widely used in clinical setting as a β-lactam antibiotic. However, the specific transporter involved in mediating AMP transport remains unidentified. Thus, we investigated whether organic anion transporters1/3 (OAT1/3) mediate the renal transport of AMP in this study. Both rOAT1/OAT3 (Slc22a6/Slc22a8) double-knockout and wild-type (WT) rats were administered AMP via intraperitoneal injection simultaneously. Following the knockout, a significant increase in AMP plasma concentration and the area under the plasma concentration-time curve (AUC) was observed, accompanied by a marked reduction in cumulative urinary excretion. OAT1/3-overexpressing cell uptake experiments demonstrated that AMP is a substrate of OAT3, with a Michaelis-Menten constant (K) of 138.6 μM and a maximum transport velocity (V) of 80.43 pmol/mg protein/min. In conclusion, AMP was identified as a substrate of OAT3, rather than OAT1. - Source: PubMed
Publication date: 2026/02/19
Liu Yu-TingGou Xue-YanGan LuMaLiu Yi-MaiMa Yan-RongWu Xin-An - This study aimed to investigate the effects of calcitriol on endogenous biomarkers taurine and pyridoxic acid (PDA) associated with the organic anion transporters Oat1 and Oat1/3, respectively, and compare these changes with those observed for the clinical substrate, methotrexate (MTX). Male rats were administered intraperitoneal (i.p.) injections of either vehicle (maize oil) or calcitriol (2.56 nmol/kg/day) for 4 consecutive days. Plasma, urine, and tissue samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Calcitriol markedly increased plasma taurine levels, decreased its urinary excretion, and reduced taurine concentrations in most tissues. In contrast, PDA exhibited only a moderate increase in plasma levels, with no significant change in urinary excretion, but a notable increase in kidney concentrations. Additional probenecid inhibition studies supported the Oat1-mediated modulation. Intravenous (i.v.) pharmacokinetic studies of taurine (10 mg/kg) revealed altered plasma exposure, clearance, and tissue distribution following calcitriol and probenecid inhibition. In addition, calcitriol significantly affected MTX pharmacokinetics, reinforcing its effect on Oat1/3 function. Taurine induced more significant changes than PDA, indicating its greater sensitivity as an endogenous biomarker for Oat1 activity. These findings highlight the modulatory effects of calcitriol on Oat-mediated transport and demonstrate the utility of taurine and PDA as translational biomarkers for investigating transporter-mediated drug-drug interactions in drug development. - Source: PubMed
Publication date: 2026/01/27
Vo Dang-KhoaNguyen Thi-Thao-LinhJoo Seul-AMaeng Han-Joo