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Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor
D Shire1, B Calandra, M Rinaldi-Carmona
1Sanofi Recherche, Centre de Labège, France.
Biochimica Et Biophysica Acta
|June 7, 1996
Summary
Researchers cloned the mouse peripheral cannabinoid receptor (mCB2), finding it similar to human CB2 (hCB2). Both receptors respond to cannabinoids like THC and anandamide, but not to CB1-specific antagonists.
Area of Science:
- Molecular Biology
- Pharmacology
- Neuroscience
Background:
- The cannabinoid receptor type 2 (CB2) is primarily found in the peripheral nervous system.
- Understanding the structure and function of peripheral cannabinoid receptors is crucial for developing targeted therapeutics.
Purpose of the Study:
- To clone and characterize the mouse peripheral cannabinoid receptor (mCB2).
- To compare the binding affinities and functional responses of mCB2 with the human ortholog (hCB2).
Main Methods:
- Cloning of mCB2 from a mouse splenocyte cDNA library.
- Expression of mCB2 in COS-3 and CHO cell lines.
- Radioligand binding assays to determine receptor affinity.
- Functional assays measuring inhibition of cAMP production.
Main Results:
- The mCB2 sequence encodes a 347-amino acid protein with 82% identity to hCB2.
- mCB2 exhibited lower affinity for WIN 55212-2 but similar affinities for CP 55,940, delta(9)-THC, and anandamide compared to hCB2.
- Both mCB2 and hCB2 mediated agonist-induced inhibition of cAMP production, unaffected by the CB1-specific antagonist SR 141716A.
Conclusions:
- The cloned mCB2 receptor shares significant structural and functional similarities with hCB2.
- mCB2 is a valid target for studying peripheral cannabinoid receptor pharmacology.
- The findings confirm the specificity of SR 141716A for CB1 receptors.