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Hsp90β positively regulates μ-opioid receptor function.
Yixin Zhang1, Peilan Zhou1, Zhen Wang2
1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing 100850, China.
Life Sciences
|April 19, 2020
Summary
Heat shock protein 90 beta (Hsp90β) positively regulates μ-opioid receptor (MOR) signaling. Inhibiting Hsp90β with 17-AAG reduces morphine tolerance and dependence, suggesting therapeutic potential.
Area of Science:
- Pharmacology
- Molecular Biology
- Neuroscience
Background:
- The μ-opioid receptor (MOR) signaling pathway is modulated by associated proteins.
- Heat shock protein 90 isoform beta (Hsp90β) was identified as a MOR-interacting protein.
Purpose of the Study:
- To investigate the role of Hsp90β in MOR signaling transduction and function.
- To explore the therapeutic potential of Hsp90β modulation in opioid treatment.
Main Methods:
- Co-immunoprecipitation and immunofluorescence confirmed Hsp90β-MOR interaction.
- In vitro and in vivo studies assessed Hsp90β's effects on MOR signaling.
- Morphine tolerance and dependence were evaluated using hot plate and CPP tests with the Hsp90β inhibitor 17-AAG.
Main Results:
- Hsp90β, not Hsp90α, interacted with MOR, enhanced by morphine.
- Hsp90β-MOR complex modulated cAMP, PKA, MOR phosphorylation, and internalization.
- 17-AAG inhibited Hsp90β-MOR interaction, reduced morphine anti-nociception, and attenuated tolerance and dependence.
Conclusions:
- Hsp90β acts as a positive co-regulator of MOR signaling through G-protein and β-arrestin pathways.
- Hsp90β modulation offers potential to improve the pharmacological profile of opiates.
- Hsp90β inhibitors like 17-AAG may reduce opioid-induced tolerance and dependence in clinical settings.
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