Schematic representation of H
S and opioid receptor interaction. The selective μ opioid receptor enkephalin analog DAMGO acts as a direct agonist of MOR leading to its activation, phosphorylation on Ser(377), co-immunoprecipitation with β arrestin and internalization (panel A and B). The selective MOR antagonist CTAP blocks the effects induced by DAMGO, while it only partially inhibits those induces by H2S. In contrast, H2S opens the KATP channels that activate the PI3K/AKT pathway leading to MOR activation, phosphorylation, co-immunoprecipitation with β arrestin and internalization, as the selective KATP channels blocker glibenclamide and the selective PI3K inhibitor LY294002 inhibit these effects (panel C and D).