For a long time, the ECS was thought to be confined to the CB1 and CB2 receptors with other receptors playing minor roles in the ECS. In recent years, this has been shown to be untrue. This paper adds to this knowledge, exploring the way that the orphan G-protein coupled receptor 55 (GPR55) is acted upon by cannabinoids, how and where it is expressed in the body, and the potential therapeutic pathways that this entails.
Here is the full scientific article if you wish to download it.
The GPR55 receptors is particularly exciting for the expansion of our knowledge of the ECS because it is not a specific endocannabinoid receptor. While most known cannabinoid ligands will bind to GPR55, it also has a specific ligand, LPI, and a high affinity for another, O-1602. A partial affinity for cannabinoids, its own specific ligands, and the potential for more that are as yet undiscovered, make GPR55 a complicated and currently confusing receptor. Its profile is not fully elucidated but is clearly an important potential for future therapies.
The difference in structure between the largely similar CB1 and CB2 receptors and the GPR55 receptor is both interesting and potentially useful. It does not bind to cannabinoids in with the same affinity as the CB receptors and this is both the reason it has taken a long time to find and elucidate, and the reason it is so exciting to scientists.
The overall effects of the ECS have been explored for some time but a distinct ECS receptor that is both in different tissues and plays different roles massively expands the potential for understanding of how the brain and other tissues grow, are regulated, and how we can possibly exploit this system for therapeutic benefit.
Cannabinoids play an important part in the proliferation of cancer cells. This is not well understood, but the authors suggest that GPR55 is a key player in the dynamics of cancerous tumours and cells. The agonist LPI is found in higher than normal concentrations in the blood plasma of patients with ovarian cancer.
The “expression of GPR55 correlates with aggressiveness” of tumours in humans. When GPR55 receptors were blockaded, the proliferation of ovarian, prostate, brain, and breast cancer cells decreased. Further evidence suggests that reducing GPR55 expression can significantly reduce proliferation and even halt the growth of cancers.
The as yet partially unexplored role of GPR55 in immune responses is possibly the reason that GPR55 knock out mice were immune to induced hyperalgesia, or extreme pain sensitivity. This suggests a very strong role in pain response and modulation via the GPR55 receptor, and presents an exciting new avenue for novel pain relieving drugs.
LPI “induced the expression of genes involved in fat deposition”. As LPI is a GPR55-specific ligand, it suggests that it might also be a target for the effective treatment of obesity. The picture of GPR55 in the body is still unclear but it is now known to be a partial cannabinoid receptor, is expressed in many different tissues, and changes how several important processes in the body work.
It is a possible target for pain relief, obesity, and the treatment of several different forms of cancer. More research is needed.