MOLECULAR-CLONING, EXPRESSION AND FUNCTION OF THE MURINE CB2 PERIPHERAL CANNABINOID RECEPTOR

We have cloned the peripheral cannabinoid receptor, mCB2, from a mouse splenocyte 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 s horter than hCB2 by 13 amino acids at the carboxyl terminus. Binding e xperiments with membranes from COS-3 cells transiently expressing mCB2 showed that the synthetic cannabinoid WIN 55212-2 had a 6-fold lower affinity for mCB2 than for hCB2, whereas both receptors showed similar affinities for the agonists CP 55,940, Delta(9)-THC and anandamide an d almost no affinity for the central receptor-(CB1) specific antagonis t SR 141716A. Both hCB2 and mCB2 mediate agonist-stimulated inhibition of forskolin-induced cAMP production in CHO cell lines permanently ex pressing the receptors SR 141716A failed to antagonize this activity i n either cell line, confirming its specificity for CB1.