Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications.

ABSTRACT: Sensitization of adenylyl cyclase (AC) signaling has been implicated in a variety of neuropsychiatric and neurologic disorders including substance abuse and Parkinson's disease. Acute activation of Gαi/o-linked receptors inhibits AC activity, whereas persistent activation of these receptors results in heterologous sensitization of AC and increased levels of intracellular cAMP. Previous studies have demonstrated that this enhancement of AC responsiveness is observed both in vitro and in vivo following the chronic activation of several types of Gαi/o-linked receptors including D2 dopamine and μ opioid receptors. Although heterologous sensitization of AC was first reported four decades ago, the mechanism(s) that underlie this phenomenon remain largely unknown. The lack of mechanistic data pre

SUBMITTER: Conley JM 

PROVIDER: S-EPMC3990329 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature