Table 9.
Comparison of OSTα/β to Other Transporters Sharing the Same Substrate(s).
| Protein | Gene(s) | Cellular Localizationa | Transport Direction | Driving Force | Transcriptional Regulation | References |
|---|---|---|---|---|---|---|
| OSTα/β | SLC51A, SLC51B | Basolateral (intestine, liver, kidney) | Uptake and Efflux | Substrate gradient | FXR, CAR, PXR, HNF1α, HNF4α, LXRα, RARα, RXRs | (Ballatori, et al., 2005; Okuwaki, et al., 2007; Petrov, et al., 2020; Schaffner, et al., 2015; Seward, et al., 2003; Teng & Piquette-Miller, 2007; Wang, et al., 2001; Xu, et al., 2014) |
| NTCP | SLC10A1 | Basolateral (liver) | Uptake | Na+-dependent (symporter) | FXR, PXR, HNF4α, RXR | (Denson, et al., 2001; Ho, et al., 2004) |
| ASBT | SLC10A2 | Apical (intestine, kidney) | Uptake | Na+-dependent (symporter) | FXR | (Craddock, et al., 1998; Hallen, et al., 2002; Kramer, et al., 1999; Love, et al., 2001) |
| OCT1 | SLC22A1 | Basolateral (intestine, kidney, liver) | Uptake and Efflux | Substrate gradient, membrane potential-influenced | PXR, PPAR, HNF1α, HNF4α | (O’Brien, et al., 2013; Saborowski, Kullak-Ublick, & Eloranta, 2006) |
| OCT2 | SLC22A2 | Basolateral (kidney) | Uptake and Efflux | Substrate gradient | HNF1, HNF4α | (Popowski, et al., 2005) |
| OAT1 | SLC22A6 | Basolateral (liver) | Uptake | Anion/Dicarboxylate exchanger | LXR, HNF1α/β | (Jin, Kikuchi, Saji, Kusuhara, & Sugiyama, 2012; Kittayaruksakul, Soodvilai, Asavapanumas, Muanprasat, & Chatsudthipong, 2012) |
| OAT2 | SLC22A7 | Basolateral (kidney, liver), apical (kidney) | Uptake and Efflux | Anion/Dicarboxylate exchanger | FXR, RARα, RXRα, HNF4α | (Fork, et al., 2011; Kobayashi, et al., 2005; Le Vee, Jouan, Stieger, & Fardel, 2013; Shen, et al., 2015) |
| OAT3 | SLC22A8 | Basolateral (kidney) | Uptake | Anion/Dicarboxylate exchanger | HNF1α/β | (Burckhardt & Burckhardt, 2011; Jin, et al., 2012; Kikuchi, et al., 2006) |
| OAT4 | SLC22A11 | Apical (kidney) | Uptake and Efflux | Anion/Dicarboxylate exchanger | HNF1α/β | (Burckhardt, 2012; Jin, et al., 2012; Zhou, et al., 2004) |
| OAT7 | SLC22A9 | Basolateral (liver) | Uptake | Fatty acid exchanger | HNF1α, HNF4α | (Klein, et al., 2010; Emami Riedmaier, et al., 2016) |
| MATE1 | SLC47A1 | Apical (kidney, liver) | Efflux (Uptake at ≥pH 7.4) | pH-dependent, H+ antiporter | HNF4α | (Lu, et al., 2010; Tanihara, et al., 2007; Tsuda, et al., 2007) |
| MATE2-K | SLC47A2 | Apical (kidney) | Efflux | pH-dependent, H+ antiporter | NA | (Tanihara, et al., 2007; Terada & Inui, 2008) |
| OATP1A2 | SLCO1A2 | Apical (intestine, liver, kidney), Basolateral (liver) | Uptake (and Efflux) | Unclear | SXR, PXR, VDR | (Eloranta, Hiller, Juttner, & Kullak-Ublick, 2012; Lee, et al., 2005; Miki, et al., 2006) |
| OATP1B1 | SLCO1B1 | Basolateral (liver) | Uptake | Substrate gradient, pH-influenced | FXR, PXR, LXRα, HNF1α, HNF3β, HNF4α | (Gui, et al., 2008; Kamiyama, et al., 2007; Ohtsuka, et al., 2006; Rodrigues, et al., 2019) |
| OATP1B3 | SLCO1B3 | Basolateral (liver) | Uptake (and Efflux) | Substrate gradient, pH-influenced | FXR, HNF1α, HNF3β, HNF4α | (Gui, et al., 2008; Kamiyama, et al., 2007; Ohtsuka, et al., 2006; Rodrigues, et al., 2019) |
| OATP2B1 | SLCO2B1 | Apical (intestine), Basolateral (liver, intestine) | Uptake | Substrate gradient, pH-influenced | FXR, PXR, HNF1α, HNF3β, HNF4α | (Hagenbuch & Stieger, 2013; Ohtsuka, et al., 2006; Rodrigues, et al., 2019; Yamada, et al., 2007) |
| OATP4C1 | SLCO4C1 | Basolateral (kidney) | Uptake | Substrate gradient | AhR | (Mikkaichi, et al., 2004; Suzuki, et al., 2011) |
| P-gp | ABCB1 | Apical (intestine, kidney, liver) | Efflux | ATP-dependent | CAR, PXR, HNF1α, VDR | (Callaghan, Crowley, Potter, & Kerr, 2008; Chan, Hoque, Cummins, & Bendayan, 2011; Chow, Durk, Cummins, & Pang, 2011; Kimura, Kioka, Kato, Matsuo, & Ueda, 2007; Rodrigues, et al., 2019) |
| MDR3 | ABCB4 | Apical (liver) | Efflux | ATP-dependent | FXR, LXR, PPAR | (Smith, et al., 2000) |
| BSEP | ABCB11 | Apical (liver) | Efflux | ATP-dependent | FXR, RXR | (Hayashi, et al., 2005; Kis, et al., 2009) |
| MRP1 | ABCC1 | Basolateral (intestine, kidney) | Efflux | ATP-dependent, GSH-influenced | PXR, CAR | (Bakos & Homolya, 2007) |
| MRP2 | ABCC2 | Apical (intestine, kidney, liver) | Efflux | ATP-dependent | FXR, CAR, PXR, HNF4α, VDR, NRF2 | (Arana, Tocchetti, Rigalli, Mottino, & Villanueva, 2016; Rodrigues, et al., 2019) |
| MRP3 | ABCC3 | Basolateral (liver, intestine, kidney) | Efflux | ATP-dependent | PXR, CAR, VDR | (Rodrigues, et al., 2019; Zeng, et al., 2000) |
| MRP4 | ABCC4 | Apical (intestine, kidney), Basolateral (liver) | Efflux | ATP-dependent, GSH-influenced | FXR, CAR, PPAR | (Lai & Tan, 2002) |
| BCRP | ABCG2 | Apical (intestine, liver) | Efflux | ATP-dependent | CAR, PXR, PPAR | (Rodrigues, et al., 2019; Lin, et al., 2017) |
a
Tissue localization: intestine, kidney and/or liver
ABC, ATP-binding cassette transporter; AhR, aryl hydrocarbon receptor; ATP, adenosine triphosphate; CAR, constitutive androstane receptor; FXR, farnesoid X receptor; GSH, reduced glutathione; HNF, hepatocyte nuclear factor; Km, substrate concentration at one-half of the maximum velocity; LXR, liver X receptor; NA, data not available in the literature; NRF2, nuclear factor erythroid-2-related factor 2; PPAR, peroxisome proliferator-activated receptor; PXR; pregnane X receptor; RAR, retinoid acid receptor; RXR, retinoid X receptor; SLC, solute carrier transporter; SXR, steroid and xenobiotic receptor; VDR, vitamin D receptor