The modulated by the CB1 and CB2

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


Puighermanal and Maldonado (2007) showed activation of AKT in the brain after
acute administration of THC, which was mediated by CB1 receptors. They used
groups of 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,
administration of the cannabinoid antagonist stopped the enhanced
phosphorylation of AKT kinase induced by THC. These results show the
involvement of the CB1 receptor in the activation of AKT pathway.


Gomez del
Pulgar, Velasco and Guzman (2000) found that the activation of AKT may be
modulated by CB1 receptor. They used Chinese hamster ovary (CHO) cells, which
were transfected with CB1 cannabinoid receptor cDNA. 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 et al. (2003) showed that THC induced the
activation of the AKT pathway through CB1 and CB2 receptors. The results showed
that THC induced an enhanced phosphorylation of Thr308 –AKT and Ser473-AKT. To
examine the role of cannabinoid receptors in AKT pathway, they used CB1 and CB2
antagonists. 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) found that the activity of the 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 phosphorylation of AKT S473.


Figure 4. AKT phosphorylation % increases
doses dependently after administration of acute THC.

From 1 THC
(mg/Kg) till 20 THC (mg/Kg), there is a significant increase in p-AKT % of


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