Fig. 5.

Canonical Gs-Gi antagonistic interaction at the AC level in the A2AR-CB1R heterotetramer. a–h Effect of TM peptides on the cAMP formation induced by forskolin (500 nM) or by the A2AR agonist CGS21680 (CGS, 500 nM) and counteractive effects of the CB1R agonist CP55940 (200 nM). HEK-293T cells were transiently transfected with the cDNAs of CB1R and A2AR (2 μg in both cases) and treated for 4 h with 4 μM of peptides TM4, TM5, TM6, or TM7 of the A2AR or CB1R. Values are means ± S.E.M. (n = 5 with triplicates in all experiments) of the percentage of forskolin-induced cAMP formation and analyzed statistically with repeated measures ANOVA, followed by Dunnett’s multiple comparison test (*, **, and ***: p < 0.05, p < 0.01, and p < 0.001, respectively, compared with basal; ^#, ^##, and ^###: p < 0.01 and p < 0.001, respectively, compared to forskolin or CGS)