The action of a negative allosteric modulator at the dopamine D₂ receptor is dependent upon sodium ions.

ABSTRACT: Sodium ions (Na⁺) allosterically modulate the binding of orthosteric agonists and antagonists to many class A G protein-coupled receptors, including the dopamine D₂ receptor (D₂R). Experimental and computational evidences have revealed that this effect is mediated by the binding of Na⁺ to a conserved site located beneath the orthosteric binding site (OBS). SB269652 acts as a negative allosteric modulator (NAM) of the D₂R that adopts an extended bitopic pose, in which the tetrahydroisoquinoline moiety interacts with the OBS and the indole-2-carboxamide moiety occupies a secondary binding pocket (SBP). In this study, we find that the presence of a Na⁺ within the conserved Na⁺-binding pocket is required for the actio

SUBMITTER: Draper-Joyce CJ 

PROVIDER: S-EPMC5775417 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature