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Co-expressions of different opioid receptor types differentially modulate their signaling via G(16)
Maurice K C Ho1, David C New, Yung H Wong
1Department of Biochemistry, Molecular Neuroscience Center and Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China.
Abstract:
Combinations of two different types of opioid receptors - delta-, kappa-, mu-opioid receptors (DOR, KOR, and MOR) and opioid receptor-like receptor 1 (ORL(1)) - were co-expressed with the alpha subunit of G(16) in COS-7 cells, and the ability of various selective agonists to induce activation of phospholipase Cbeta was examined. Nociceptin/orphanin FQ-induced response was enhanced when ORL(1) was co-expressed with MOR or KOR but not DOR. The kappa-agonist U50,488H induced a modest inositol phosphate formation when KOR was expressed alone or with MOR, but the response was attenuated when co-expressing with either DOR or ORL(1). It is suggested that the co-expressions of two different opioid receptor types indeed modify their downstream signaling events.
Insights
Co-expressing opioid receptors like delta-, kappa-, and mu-opioid receptors (DOR, KOR, MOR) with opioid receptor-like receptor 1 (ORL1) alters their signaling pathways. These combinations impact downstream events, particularly phospholipase Cbeta activation.
Area of Science:
- Pharmacology
- Molecular Biology
- Neuroscience
Background:
- Opioid receptors (delta-, kappa-, mu-opioid receptors - DOR, KOR, MOR) and opioid receptor-like receptor 1 (ORL(1)) are G protein-coupled receptors involved in pain and other physiological processes.
- Understanding their signaling pathways is crucial for developing targeted therapeutics.
- The downstream signaling of these receptors, particularly their interaction when co-expressed, is not fully elucidated.
Purpose of the Study:
- To investigate how co-expression of different opioid receptor types (DOR, KOR, MOR) with ORL(1) affects their downstream signaling.
- To examine the activation of phospholipase Cbeta (PLCbeta) in response to selective agonists when these receptors are combined.
Main Methods:
- COS-7 cells were utilized for co-expression studies.
- Combinations of DOR, KOR, MOR, and ORL(1) were expressed with the alpha subunit of G(16).
- The ability of selective agonists to induce phospholipase Cbeta activation was measured using inositol phosphate formation assays.
Main Results:
- Nociceptin/orphanin FQ-induced signaling was enhanced when ORL(1) was co-expressed with MOR or KOR, but not DOR.
- The kappa-agonist U50,488H elicited a modest response when KOR was expressed alone or with MOR.
- This kappa-agonist response was attenuated when KOR was co-expressed with DOR or ORL(1).
Conclusions:
- Co-expression of different opioid receptor types significantly modifies their downstream signaling events.
- The interactions between opioid receptors and ORL(1) can lead to either potentiation or attenuation of signaling pathways.
- These findings highlight the complex interplay of opioid receptor signaling and suggest potential for novel therapeutic strategies.