n nuclear pAkt to that observed for PEA treated cells, indicating that PEAs effects were not mediated through SKI-606 SKI-606 380843-75-4 380843-75-4 CB2 receptor activation. Interestingly, combined treatment with PEA and AM630 led to an increase in nuclear pAkt relative to cytosolic pAkt immunoreactivity in part due to a decrease in cytosolic pAkt immunoreactivity. These results suggest that alterations in Akt and pAkt compartmentalization are affected differently by PEA and AM630. These results provide evidence that CB2 activation is not responsible for the observed changes in pAkt immunoreactivity mediated by PEA treatment in HT22 cells.
Exposure of HT22 cells to PEA for 30 minutes had no effect on ERK1/2 immunoreactivity.
Exposure of cells to PEA for 30 minutes, however, led to a significant increase in nuclear and cytosolic pERK1/2 immunoreactivity. Exposure of cells to PEA for 60 minutes resulted in a dramatic and significant decrease in both nuclear and cytosolic phospho p38 immunoreactivity. buy SKI-606 Furthermore, treatment of HT22 cells with JWH015 had no buy SKI-606 significant effect on ERK1/2 or pERK1/2 immunoreactivity. This suggests that PEAs effects on ERK1/2 and pERK1/2 immunoreactivity are not due to CB2 activation. From these studies, we conclude that PEA protects HT22 cells from oxidative stress when cells are pretreated for 5 6 hours prior to tBHP exposure.
Interestingly, shorter PEA pretreatment times did not protect and PEA pretreatment for 12 hours protected cells from tBHP insult as measured by G 6 PD activity in the culture media.
These studies identify PEA as a neuroprotectant that is naturally synthesized in neurons. In addition, we provide evidence that PEA treatment facilitates the nuclear translocation of pAkt in a neuronal cell line by a CB2 independent mechanism. Furthermore, we determined that PEA leads to a rapid and transient increase in nuclear and cytosolic pERK1/2, but not ERK1/2. This mechanism is independent of Cannabis sativa has been used for both medicinal and recreational purposes throughout recorded history.
The discovery by Gaoni and Mechoulam of Δ9 tetrahydrocannabinol, the major psychoactive ingredient in marijuana, ushered in a new era of research focused on understanding the functional roles of cannabinoid receptors in the nervous system.
The cloning of cannabinoid CB1 and CB2 receptors and isolation of their endogenous ligands marked a transition in the cannabinoid field. Cannabinoids could no longer be thought of merely as illicit drugs of abuse, but rather represented pharmacological tools for studying the functional roles of CB1 and CB2 receptors in the nervous system. Activation of cannabinoid CB1 and CB2 receptors suppresses pathological pain in animal models. CB1 receptors are localized primarily within the central nervous system and are associated with the rewarding aspects of several addictive compounds including nicotine, alcohol, and cocaine. Activation of CB1 receptors produces hypothermia, motor ataxia, catalepsy, and hypoactivity. The discovery of the CB2 receptor opened the door to exploring the role of this receptor as a therapeutic target for pain and inflammation. CB2 receptors are localized preferentially, but not exclusively, to immune cells in the periphery and