The The results showed that AKT phosphorylation(inactivation) increased


activation of AKT pathway is regulated by cannabinoids (receptors) in the


Puighermanal and Maldonado (2007) showed inactivation of AKT in the brain because
of THC, which was mediated by CB1 receptors. They used mice, who received
different doses of THC. The results showed that AKT
phosphorylation(inactivation) increased dose dependently (figure 4, Ozaita et al.,2007,1109 ). Furthermore, a cannabinoid
antagonist stopped the enhanced phosphorylation of AKT induced by THC. These
results indicate the involvement of CB1 receptors in the AKT pathway.


del Pulgar, Velasco and Guzman (2000) also found that the activation of AKT might
be regulated by CB1 receptor. They used Chinese hamster ovary (CHO) cells,
those were transfected with cDNA of CB1. These cells were for different times
treated with THC. The results showed that THC induced a time-dependent
stimulation of AKT. These data demonstrate the involvement of the CB1 receptor
in the THC-induced stimulation of AKT.  Not only the CB1 receptor has a role in the
AKT pathway. Sanchez, Ruiz-Llorente, Sanchez and Diaz-Laviada (2003) showed
that THC induced the activation of the AKT pathway through CB1 and CB2
receptors. The results showed that THC induced an enhanced inactivation of
Ser473/Thr308-AKT. They used CB1 and CB2 antagonists, to examine the role of
cannabinoid receptors in AKT pathway. They investigated that both antagonists
were able to inhibit the cannabinoid-induced phosphorylation of AKT. These data
may indicate that the AKT pathway is activated by the cannabinoid receptors,
CB1 and CB2. In addition, Molina-Holgado et al. (2004)also supported the idea
that the activity of AKT pathway was modulated by the CB1 and CB2 receptors. To
examine the contribution of the cannabinoid receptors they used CB1 and CB2
antagonist. Also, as a marker of AKT activity they used phosphorylation of
S473.The results showed that both the antagonist prevented the inactivation of
AKT S473