9.A.14.13.18
Mu-type opioid receptor of 400 aas and 7 TMSs, OprM1. Receptor for endogenous opioids such as beta-endorphin and endomorphin and for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity as well as both N-type and L-type calcium channels, and activation of inward rectifying potassium channels (Knapman and Connor 2015). Activation of the astrocytic μ-opioid receptor elicits fast glutamate release through TREK-1-containing K2P channel in hippocampal astrocytes (Woo et al. 2018).