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
- 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 - Kidney drug transporters, primarily located in the basolateral and apical membranes of proximal tubule cells, play a key role in the secretion and reabsorption of drugs and endogenous compounds. Recent studies have demonstrated that kidney diseases can alter transporter expression; however, the expression of these transporters in human transplanted kidneys, with and without rejection, remains unclear. Therefore, the aim of this study was to investigate the mRNA expression (qRT-PCR) and immunolocalization (via immunohistochemistry) of key ABC (ATP-binding cassette) (n = 14) and SLC (solute carriers) (n = 33) transporters in glomeruli and proximal tubule cells from human normal kidney (CTRL, n = 8), non-rejected transplanted kidney (AR-0, n = 7) and transplanted kidney under rejection process (AR-I, n = 8) from patients receiving immunosuppressive drugs. Our study shows that mRNA expression level of SLC22A4, SLC22A6, SLC22A7, SLC22A8, SLC28A1, SLC47A1, SLC22A11, SLC15A2, SLC16A1, ABCC2, ABCC5 and ABCC6 are statistically significantly downregulated, while SLC22A2, SLCO4A1 and ABCB1 are statistically upregulated in proximal tubule cells from rejected transplanted kidneys compared to controls. Immunohistochemistry revealed that OAT1, OAT3, OCT2, MATE1, MRP2, MRP6 and P-gp were primarily expressed in proximal tubule cells, with significantly lower protein expression of OAT1, OAT3, P-gp in AR-I and AR-0 biopsies compared to CTRL sections. These preliminary data suggest that the expression profile of kidney transporters may be altered in transplanted kidneys from patients treated with immunosuppressive drugs. - Source: PubMed
Publication date: 2026/01/23
Łapczuk-Romańska JHybiak JPiotrowska KMarchelek-Myśliwiec MWilk ASłojewski MUrasińska EDroździk M