title: Kir3 channel signaling complexes: focus on opioid receptor signaling.
abstract: Opioids are among the most effective drugs to treat severe pain. They produce their analgesic actions by specifically activating opioid receptors located along the pain perception pathway where they inhibit the flow of nociceptive information. This inhibition is partly accomplished by activation of hyperpolarizing G protein-coupled inwardly-rectifying potassium (GIRK or Kir3) channels. Kir3 channels control cellular excitability in the central nervous system and in the heart and, because of their ubiquitous distribution, they mediate the effects of a large range of hormones and neurotransmitters which, upon activation of corresponding G protein-coupled receptors (GPCRs) lead to channel opening. Here we analyze GPCR signaling via these effectors in reference to precoupling and collision models. Existing knowledge on signaling bias is discussed in relation to these models as a means of developing strategies to produce novel opioid analgesics with an improved side effects profile.
authors: Département de Pharmacologie, Faculté de Médecine, Université de Montréal Montreal, QC, Canada ; Centre de Recherche du CHU Sainte-Justine Montréal, QC, Canada.
authors: Karim
authors: K
authors: Nagi
authors: Département de Pharmacologie, Faculté de Médecine, Université de Montréal Montreal, QC, Canada ; Centre de Recherche du CHU Sainte-Justine Montréal, QC, Canada ; Département de Psychiatrie, Faculté de Médecine, Université de Montréal Montréal, QC, Canada.
authors: Graciela
authors: G
authors: Pineyro
keywords: GIRK; allosteric modulation; analgesia; bias; functional selectivity; opioid; signaling; signaling complexes