Neuropeptide oxytocin enhances μ opioid receptor signaling as a positive allosteric modulator

Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Yoshiyuki Meguro, Kanako Miyano, Shigeto Hirayama, Yuki Yoshida, Naoto Ishibashi, Takumi Ogino, Yuriko Fujii, Sei Manabe, Moeko Eto, Miki Nonaka, Hideaki Fujii, Yoichi Ueta, Minoru Narita, Naohiro Sata, Toshihiko Yada, Yasuhito UezonoAbstractOxytocin (OT) is a 9-amine neuropeptide that plays an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. OT has been reported to exert an analgesic effect in both humans and animals, and the results of certain animal experiments have shown that the analgesic effect of OT is partially blocked by opioid receptor antagonists. To investigate the relationship between OT and μ opioid receptor (MOR), we evaluated how OT affects MOR in vitro by performing an electrical impedance-based receptor biosensor assay (CellKey™ assay), an intracellular cAMP assay, and a competitive receptor-binding analysis by using cells stably expressing human MOR and OT receptor. In both the CellKey™ assay and the intracellular cAMP assay, OT alone exerted no direct agonistic effect on human MOR, but treatment with 10−6 M OT markedly enhanced the MOR signaling induced by 10−6 M endomorphin-1, β-endorphin, morphine, fentanyl, and DAMGO. Moreover, in the competitive receptor-binding assay, 10−6 M OT did not alter the affinity of endomorphin-1 or morphine for MOR. These results suggest that OT could function as a positiv...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research