Bile acids inhibit equilibrative adenosine transport to alter adenosine receptor signaling in cholestasis.

ABSTRACT: High plasma bile acid (BA) levels in individuals with cholestasis affect adenosine (Ado) receptor (AdoR) signaling, but the underlying mechanisms are unclear. Here, we investigated BA interference with cellular Ado transport as a putative mechanism for altering extracellular Ado availability for AdoR signaling. Computational modeling and experimental studies revealed that equilibrative nucleoside transporter 2 (ENT2), but not ENT1, is capable of translocating BAs across the mammalian plasma membrane. ENT2-mediated BA transport has low affinity, is pH independent, and is partially sensitive to inhibition by nitrobenzylthioinosine (NBMPR). At cholestatic plasma concentrations of BAs, however, BAs interfere with Na⁺-independent, NBMPR-sensitive, ENTs without affecting Na⁺

SUBMITTER: Joshi A 

PROVIDER: S-EPMC12152883 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature