Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor

摘要

We have cloned the peripheral cannabinoid receptor, mCB2, From a mouse splenoeyte cDNA library. The 3.7 kb sequence contains an open reading frame encoding a protein of 347 residues sharing 82% overall identity with the only other known peripheral receptor, human CB2 (hCB2) and shorter than hCB2 by 13 amino acids at the carboxyl terminus. Binding experiments with membranes IVom C'OS-3 cells transiently expressing mCB2 showed that the synthetic cannabinoid WIN 55212-2 had a n-lbld lower al'l'inity For m('B2 than For hCB2, whereas both receptors showed similar affinities for the agonists CP 55,940, zV'-THC and anandamide and almost no affinity For the central receptor- (CB1) specific antagonist SR 141716A. Both hCB2 and mCB2 mediate agonist-stimulated inhibition of forskolin-in-duced cAMP production in CHO cell lines permanently expressing the receptors. SR 141716A Failed to antagonize (his activity in either cell line, confirming its specificity for CB1.