C9 〇Nuttawadee Ngamlertwong¹、土屋 裕義¹、藤原 葉子¹、東 森生¹、輿水 崇鏡¹ Ngamlertwong Nuttawadee¹, Tsuchiya Hiroyoshi¹, Fujiwara Yoko¹, Morio Azuma¹, Taka-Aki Koshimizu^{1 1}自治医科大・医・分子薬理 It is difficult in characterizing heteromer-specific functions of G-protein coupled receptors (GPCRs) and finding a chemical that can act on the specific heteromers. Heteromeric GPCRs may have a new character, which is not shared between each participating receptor. The difficulty associated with the analysis of heteromeric receptors partly comes from the fact that homomeric receptors formed by the protomer of heteromer receptor co-exist with heteromeric receptors in a cell. We recently discovered that opioid signal originating from morphine uses heteromer receptor between mu-type opioid receptor and V1b vasopressin receptor in a beta-arrestin-dependent way to generate analgesic tolerance. Here, we report a method to detect three molecule interactions using split luciferase and a fluorescence protein as a BRET (bioluminescence resonance energy transfer) acceptor. This method allowed us to sensitively monitor access of beta-arrestin specifically to the heteromeric or homomeric receptors. Therefore, our system provides a screening method for a chemical that can reduce development of morphine tolerance during pain management.