S-Nitrosoglutathione Is Not a Substrate of OATP1B1, but Stimulates Its Expression and Activity.

S-nitrosoglutathione (GSNO) is the S-nitrosated derivative of glutathione (GSH). GSNO is an endogenous class of NO donors and a natural NO depot in biological systems. Organic anion transporting polypeptide 1B1 (OATP1B1) is an influx transporter that is expressed in the liver. OATP1B1 plays an important role in the transport of endogenous and exogenous substances. Various pathways for the regulation of OATP1B1 have been described. In the present study, the involvement of OATP1B1 in GSNO transport and the regulation of OATP1B1 by GSNO was examined. For HEK293-OATP1B1, it has been shown that GSNO is not a substrate of OATP1B1, but OATP1B1 can participate in the transport of GSH across the cell membrane. GSNO at concentrations of 1-100 μM and exposure for 3 h do not affect the expression and activity of OATP1B1, but exposure for 24 and 72 h stimulates the expression of the SLCO1B1 gene, OATP1B1, and transporter activity. Up-regulation of OATP1B1 by GSNO is carried out through the NO-cGMP signaling pathway, Nrf2, and LXRa.