The role of RGS12 in differential modulation of G protein versus beta-arrestin signaling downstream of the kappa opioid receptor

Project Narrative (Public Health Relevance): Chronic pain, drug addiction, anxiety and depression each extract substantial health and socioeconomic costs from the American populace. Although drugs directed toward the kappa opioid receptor (KOR) have been investigated as treatments for these human ailments, they are currently hampered by poor side effect profiles. A deeper understanding of the mechanisms by which the proteins RGS12 and β-arrestin2 regulate the beneficial versus detrimental effects of KOR-directed drugs will enable new strategies to maximize the clinical utility of these (and future) drugs that provide pain relief by targeting opioid receptors, but without addiction or side effect liabilities.