Ask about this productRelated genes to: SLC22A6 antibody
- 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 antibody
Related articles to: SLC22A6 antibody
- The arachnoid mater-forming cells, which exhibit expressions of organic anion and cation transporters, as well as tight junction proteins, form the blood-arachnoid barrier. The purpose of the present study was to clarify the roles of the arachnoid mater transporters in the cerebrospinal fluid (CSF) clearance of prostaglandin D (PGD) and metformin by using an intracisternal administration method for evaluating arachnoid mater-mediated transport in rats. Global proteomics of rat leptomeninges showed the transporter expression of Slc22a6/Oat1, Slc22a8/Oat3, Slco2a1/Oatp2a1, Slc22a2/Oct2, and Slco2b1/Oatp2b1. The CSF clearance of PGD and metformin was greater than that of FITC-inulin, which is a marker of CSF bulk flow and parenchymal diffusion. The CSF elimination of PGD was significantly inhibited by p-aminohippuric acid, diclofenac (substrates/inhibitors of Slc22a6/Oat1 and Slc22a8/Oat3), and taurocholate (a broad substrate/inhibitor of Slco family transporters), whereas that of metformin was blocked by cimetidine, tetraethylammonium, and thiamine (substrates/inhibitors of Slc22a2/Oct2). The CSF-to-circulating blood transfer of metformin was inhibited by tetraethylammonium. These results suggested that the PGD clearance from the CSF most likely occurred via Slc22a6/Oat1, Slc22a8/Oat3, Slco2a1/Oatp2a1, and Slco2b1/Oatp2b1, while the metformin clearance was primarily mediated by Slc22a2/Oct2, in the arachnoid mater. These transporters would regulate the CSF concentrations of pharmacologically active substances and drugs. - Source: PubMed
Publication date: 2026/04/17
Yaguchi YukaSasaki KazunariInagaki MaiTerasaki TetsuyaTachikawa Masanori - Short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) include small organic anions derived from the gut microbiome that interact with organic anion transporters of the SLC22 family, many of which are expressed in the kidney proximal tubule. According to the Remote Sensing and Signaling Theory (RSST), crosstalk between organs (e.g., gut-liver-kidney axis, gut-brain axis) and the gut microbiome is mediated by metabolites and signaling molecules transported by multi-specific "drug" transporters. The renal drug transporter OAT1 (SLC22A6) is also a major transporter of gut-microbiome products and uremic toxins (e.g., indoxyl sulfate); it has been shown to act as part of a regulatory feedback loop involving the gut microbiome. SCFAs, especially propionate and butyrate, have been shown to play a central role in the transcriptional regulation of OAT1 through HDAC inhibition. By fecal metagenomics analyses of knockout mice, we now find that propionate synthesis is among the most altered pathways in the gut microbiome. In contrast, these pathways were only minimally altered in the Oat3 (Slc22a8) knockout. Metabolomics analyses indicate that serum propionate derivatives (e.g., propionyl glycine) and 3-hydroxybutyrate are dependent on OAT1 in the knockout mice and in humans treated with probenecid, an OAT1 inhibitor. The gut microbiome of the knockout mice also exhibited greater fatty acid synthesis, which generates odd-chain-length fatty acids (e.g. heptanoate) when propionate is available. Overall, the data, especially when considered in light of in vitro experiments of others, indicates the in vivo existence of a feedback loop connecting gut-microbiome-derived SCFAs and MCFAs to kidney proximal tubule uptake via OAT1. This bidirectional feedback loop in turn regulates OAT1 expression through HDAC inhibition. The feedback loop is clearly consistent with the Remote Sensing and Signaling Theory-in particular, the centrality of multi-specific "drug" transporters in organ crosstalk and host-microbiome interactions via small molecules with "high information content." The key role of OAT1 function in maintaining tubular secretion in CKD supports the importance of this RSST loop in renal pathophysiology. Modulating this RSST loop could have therapeutic value in chronic kidney disease and other contexts. - Source: PubMed
Publication date: 2026/05/29
Ermakov Vladimir SFalah KianNigam Sanjay K - The gut microbiome plays a key role in tryptophan metabolism by directly generating indole derivatives and indirectly modulating the host-driven kynurenine pathway via microbial metabolites. In this study, we examined the effects of 12 gut microbiome-related tryptophan metabolites on major drug transporters. In vitro assays using transporter-overexpressing cell lines revealed that indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), kynurenic acid (KA), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (HAA) inhibited organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) activity by up to 83.7%, with half-maximal inhibitory concentration (IC) values ranging from 5.41 to 121 μM for OAT1 and 0.31 to 9.50 μM for OAT3. Molecular docking analysis provided qualitative support for potential interactions with OAT1. In vivo pharmacokinetic studies in rats showed that the coadministration of these metabolites significantly increased systemic exposure of furosemide, a representative OAT1/OAT3 substrate, by 1.3- to 2.9-fold and was accompanied by changes in renal excretion. In contrast, most metabolites showed minimal effects on other transporters such as organic anion transporting polypeptide 1B1/1B3 (OATP1B1/OATP1B3), organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), multidrug resistance protein 1 (MDR1), and breast cancer resistance protein (BCRP). These findings provide mechanistic in vitro evidence that selected gut microbiome-related tryptophan metabolites interact with OAT1/OAT3 and proof-of-concept rat pharmacokinetic data showing altered furosemide disposition after metabolite coadministration. Further studies are required to determine whether these transporter-related effects are clinically relevant in humans. - Source: PubMed
Publication date: 2026/05/13
Kang Min-JiLee Kyeong-RyoonKim Min JuJeong Hyeon-CheolChae Yoon-Jee - 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