Assessing Opioid Regulation of Adenylyl Cyclase Activity in Intact Cells

Modulation of adenylyl cyclase activity constitutes one of the important intracellular signaling cascades by which many receptors, including opioid receptors, translate extracellular messages into cellular function. Following receptor activation, adenylyl cyclase is either activated or inhibited via the α-subunit of G_s or G_i/o protein, respectively (1 ). Regulation of adenylyl cyclase activity consequently leads to changes in intracellular levels of adenosine 3′, 5′-cyclic monophosphate (cAMP), which, in turn, activates cAMP-dependent protein kinase (2 ). Opioid receptor coupling to adenylyl cyclase is commonly exploited to study the responsiveness to opioid ligands at the cellular level. In most of the cell systems studied, acute activation of opioid receptors leads to inhibition of adenylyl cyclase activity and a decrease in intracellular cAMP levels (3 ).