Anandamide and WIN 55212-2 inhibit cyclic AMP formation through G-protein-coupled receptors distinct from CB1 cannabinoid receptors in cultured astrocytes

The effects of anandamide and the cannabinoid receptor agonists WIN 55212-2 and CP 55940 on the evoked formation of cyclic AMP were compared in cultur ed neurons and astrocytes from the cerebral cortex and striatum of mouse em bryos. The three compounds inhibited the isoproterenol-induced accumulation of cyclic AMP in neuronal cells, and these responses were blocked by the s elective CB1 receptor antagonist SR 141716A. The three agonists were more p otent in cortical than striatal neurons. Interestingly, WIN 55212-2, CP 559 40 and anandamide also inhibited the isoproterenol-evoked accumulation of c yclic AMP in astrocytes but, in contrast to WIN 55212-2 and CP 55940, anand amide was much more potent in striatal than cortical astrocytes. Inhibition was prevented by pertussis toxin pretreatment, but not blocked by SR 14171 6A. Therefore, G-protein-coupled receptors, distinct from CB1 receptors, ar e involved in these astrocytic responses. Moreover, specific binding sites for [H-3]-SR 141716A were found in neurons but not astrocytes. Furthermore, using a polyclonal CB1 receptor antibody, staining was observed in striata l and cortical neurons, but not in striatal and cortical astrocytes. Taken together, these results suggest that glial cells possess G-protein-coupled receptors activated by cannabinoids distinct from the neuronal CB1 receptor , and that glial cells responses must be taken into account when assessing central effects of cannabinoids.