Racemic salsolinol and its enantiomers act as agonists of the µ-opioid receptor by activating the Gi protein-adenylate cyclase pathway

Abstract

© 2017 Berríos-Cárcamo, Quintanilla, Herrera-Marschitz, Vasiliou, Zapata-Torres and Rivera-Meza. Background: Several studies have shown that the ethanol-derived metabolite salsolinol (SAL) can activate the mesolimbic system, suggesting that SAL is the active molecule mediating the rewarding effects of ethanol. In vitro and in vivo studies suggest that SAL exerts its action on neuron excitability through a mechanism involving opioid neurotransmission. However, there is no direct pharmacologic evidence showing that SAL activates opioid receptors. Methods: The ability of racemic (R/S)-SAL, and its stereoisomers (R)-SAL and (S)-SAL, to activate the µ-opioid receptor was tested in cell-based (light-emitting) receptor assays. To further characterizing the interaction of SAL stereoisomers with the µ-opioid receptor, a molecular docking study was performed using the crystal structure of the µ-opioid receptor. Results: This study shows that SAL activates the µ-opioid receptor by the classical G