Figure 4. Hepatocellular bile acid transporters. Basolateral import of bile acids is mediated by NTCP (Na⁺-dependent) and OATP isoforms (Na+-independent). Bile acids are exported through the basolateral exporters MRP3, MRP4, and the OSTα and OSTβ heterodimer and through the canalicular exporters BSEP, MRP2, and possibly MDR1. Bile acids regulate their own efflux through hepatic farnesoid X receptor (hFXR). Bile acid-activated hFXR induces the OSTα and OSTβ heterodimer and MRP2 and, as heterodimer with RXR, BSEP. hFXR also activates SHP that inhibits the importers NTCP, the OSTα and OSTβ heterodimer, LXR, and LRH-1. LXR and LRH-1 normally inhibit CYP7A1, CYP8B1, and CYP27A1, but because of SHP activation by hFXR and consequent inhibition of LRH-1 and LXR, bile acids are synthesized from cholesterol. Additionally, LRH-1 normally stimulates the expression of BSEP and the OSTα and OSTβ heterodimer, while induction of SHP by hFXR results in inhibition of those exporters. Abbreviations: BA, bile acid; BSEP, bile salt export pump; CAR, constitutively active/androstane receptor; CYP, cytochrome p450; hFXR, hepatic farnesoid X receptor; LRH-1, liver receptor homolog 1; LXR, liver X receptor; MDR1, multidrug resistance associated protein 1; MRP3/4, multidrug resistance protein 3 and 4; NTCP, Na+-taurocholate co-transporting polypeptide; OATP, organic anion transporting polypeptide; OSTα/β, organic solute transporter alpha/beta; PXR, pregnane X receptor; RXR, retinoid X receptor; SHP, small heterodimer partner.