BioAcyl Corp
BioAcyl Corp |
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Miyano, K., Yoshida, Y., & Hirayama, S. (2021). Oxytocin is a positive allosteric modulator of κ-opioid receptors but not δ-opioid receptors in the g protein signaling pathway. Cells, 10(10), 2651. Added by: Dr. Enrique Feoli (24/11/2023, 18:24) Last edited by: Dr. Enrique Feoli (24/11/2023, 18:26) |
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| Resource type: Journal Article DOI: 10.3390/cells10102651 ID no. (ISBN etc.): 2073-4409 BibTeX citation key: Miyano2021 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Oxytocin analgesia Creators: Hirayama, Miyano, Yoshida Collection: Cells |
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| Abstract |
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Oxytocin (OT) influences various physiological functions such as uterine contractions, maternal/social behavior, and analgesia. Opioid signaling pathways are involved in one of the analgesic mechanisms of OT. We previously showed that OT acts as a positive allosteric modulator (PAM) and enhances μ-opioid receptor (MOR) activity. In this study, which focused on other opioid receptor (OR) subtypes, we investigated whether OT influences opioid signaling pathways as a PAM for δ-OR (DOR) or κ-OR (KOR) using human embryonic kidney-293 cells expressing human DOR or KOR, respectively. The CellKeyTM results showed that OT enhanced impedance induced by endogenous/exogenous KOR agonists on KOR-expressing cells. OT did not affect DOR activity induced by endogenous/exogenous DOR agonists. OT potentiated the KOR agonist-induced Gi/o protein-mediated decrease in intracellular cAMP, but did not affect the increase in KOR internalization caused by the KOR agonists dynorphin A and (-)-U-50488 hydrochloride (U50488). OT did not bind to KOR orthosteric binding sites and did not affect the binding affinities of dynorphin A and U50488 for KOR. These results suggest that OT is a PAM of KOR and MOR and enhances G protein signaling without affecting β-arrestin signaling. Thus, OT has potential as a specific signaling-biased PAM of KOR.
Added by: Dr. Enrique Feoli |