The dopaminergic D receptor: Another example of reductive activation?

We have previously suggested that several intercellular messengers activate their receptors via reductive activation. Adenylate cyclase activation involves exposure of a sulfhydryl group. The dopamine D₁ receptor activates this enzyme. Because sulfhydryl exposure could be secondary to reduction of a disulfide group we evaluated dopaminergic D₁ agonists and antagonists as reducing agents. The agonists were found to be reducing agents and the antagonists were inactive. These results are consistent with the concept that dopaminergic D₁ agonists activate adenylate cyclase via reductive activation.