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1. Introduction
2. Opioid receptors
3. Alternative pre-mRNA splicing
4. Evidence: multiple mu opioid receptors
5. Alternative splicing of the mu opioid receptor gene, OPRM1
6. The mouse OPRM1 gene: C-terminal full-length 7TM splice variants
7. Truncated 6-TM splice variants
8. Truncated 1-TM splice variants
9. The three variants: summary
10. Biased signaling at a single GPCR with different agonists
11. Biased signaling at several splice variants of the same gene with a single agonist
12. Morphine actions on mMOR-1, mMOR-1C & mMOR-1O
13. Alternative splicing of the mu opioid receptor gene, OPRM1 (1)
14. Differential expressions of mu receptor splice variant mRNAs in brain of four mouse strains
15. Differential distribution of E4-associated variants (MOR-1) and E7-associated variants (MOR-1C)
16. Alternative splicing of the mu opioid receptor gene, OPRM1 (2)
17. Oprm1 Gene targeting mouse models
18. Gene targeting strategy for C-terminal tails
19. C-terminal truncation mouse models (1)
20. Morphine tolerance and physical dependence in inbred mouse strains
21. C-terminal truncation mouse models (2)
22. Expression of variant mRNAs by RT-qPCR
23. Saturation studies with [3H]DAMGO and [3H]naloxone
24. MOR-derived endocytic recycling sequence (MRS)
25. Morphine behavioral studies
26. Radiant heat tail flick assay
27. Morphine analgesia by cumulative dose-response curve
28. Morphine tolerance
29. Morphine dependence: naloxone-precipitated withdrawal
30. Morphine reward: conditioned place preference (CPP)
31. Effect of a vivo-morpholino antisense oligo on morphine tolerance and dependence in CD-1 mice
32. Loss of morphine-induced desensitization of mu receptors in the hypothalamus and brainstem
33. Comparison among the mutant mouse models
34. Signaling bias
35. A predicted phosphorylation code for high-affinity β-arrestin binding: PxPxxP/E/D or PxxPxxP/E/D
36. Summary
37. Acknowledgements

Topics Covered

• Extensive alternative pre-mRNA splicing of the mu opioid receptor gene (OPRM1)
• Distinct intracellular C-terminal tails in different full-length 7TM C-terminal variants
• Distinct in vivo functions of several C-terminal tails
• In vivo truncation of C-terminal tails encoded by E7 affects morphine tolerance and reward
• In vivo truncation of C-terminal tails encoded by E4 affects morphine tolerance and dependence

Links

Series:

• G Protein-Coupled Receptors (GPCRs) signaling in health and disease

Categories:

• Biochemistry
• Cell Biology

Talk Citation

Publication History

• Published on May 31, 2020

Financial Disclosures

• Ying-Xian Pan is a co-scientific founder of Sparian Biosciences.