Abstract

Natsuyo Akuzawa , Hideru Obinata , Takashi Izumi and Shigeki Takeda

MrgX2 is reported to be expressed in a specific subset of dorsal root ganglion sensory neurons, and it is activated by the endogenous peptides, cortistatin and proadrenomedullin N-terminal peptide. Here, we show that morphine but not opioid peptides stimulated a dose-dependent increase of the intracellular calcium ion level in MrgX2-expressing cells. Naloxone, an opioid receptor antagonist, did not influence these reactions. It was previously reported that the -opioid receptor did not show morphine dependent desensitization and internalization. In contrast, we detected morphine induced MrgX2 desensitization and internalization. Since MrgX2 gave a similar EC50 value for morphine with the - and - opioid receptors, we consider that MrgX2 could be the physiological morphine receptor. It was reported that some morphine effects (e.g., morphine-induced hyperalgesia) were observed even in the presence of an opioid receptor antagonist. Therefore, we propose the importance of studying MrgX2 together with the classical opioid receptors for the investigation of morphine effects.