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Updated: May 17, 2026
09:39
Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
EGFR dependent subcellular communication was responsible for morphine mediated AC superactivation
Hui Zhao1, Gencheng Wu, Xiaoding Cao
1Department of Integrative Medicine and Neurobiology, National Key lab of Medical Neurobiology, Institute of Brain Research Sciences, Shanghai Medical College, Fudan University, PR China. zhaohui07054@fudan.edu.cn
Cellular Signalling
|November 13, 2012
Summary
Morphine tolerance and dependence involve EGFR-mediated signaling. Chronic morphine sensitizes EGFR, promoting CRT-MOR tethering and adenylyl cyclase superactivation, crucial for synaptic organization and drug adaptation.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Compensatory adenylyl cyclase (AC) superactivation is linked to morphine tolerance and dependence.
- This mechanism involves c-Src-dependent upregulation of AC5 within lipid rafts.
Purpose of the Study:
- To investigate the role of EGFR signaling in morphine tolerance and dependence.
- To elucidate the mechanism of CRT-MOR tethering and AC5 superactivation.
Main Methods:
- Examined EGFR phosphorylation and translocation into the ER following chronic morphine treatment.
- Investigated the role of EGFR phosphorylation in CRT-MOR tethering within lipid rafts.
- Assessed the impact of EGFR signaling on AC5 superactivation and synaptic clustering.
Main Results:
- Chronic morphine treatment sensitized EGFR signaling, increasing EGFR phosphorylation and ER translocation.
- EGFR phosphorylation was essential for CRT-MOR tethering in lipid rafts, leading to AC5 superactivation.
- Synaptic clustering of CRT-MOR depended on EGFR phosphorylation, suggesting a role in synaptic organization.
Conclusions:
- Adaptive changes in MOR and EGFR signaling establish CRT-related subcellular communication.
- The proposed signaling network within the brain synaptic zone implicates in morphine tolerance and dependence.
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