GPR55 could be responsible for changes in Ca2+ and Zn2+ signaling produced by CBD and AEA (Bouron, 2018)
In a rat model of autism (Valproic Acid model), GPR55, PPARα and PPARγ were reduced in several brain regions involved in higher cognitive functions (frontal cortex and hippocampus) (Kerr et al., 2013).
GPR55 is downregulated in mice after chronic restraint stress and its activation reduced anxiety-like behaviors, involving also PLC-PKC and RhoA-ROCK pathways (Shi et al., 2017)
Until now, we know that human bladder cells express the cannabinoid receptors CB1, CB2 and GPR55 (Bakali et al., 2014).
The specific cannabinoid receptors CB2 and GPR55 are overexpressed in glioblastomas compared to non-cancer glial cells. This overexpression is also related to the prognosis of the disease, with higher overexpression of CB2 in the most aggressive tumors (Calatozzolo et al., 2007; Ellert-Miklaszewska et al., 2007; Sánchez et al., 2001).
Anandamide and CB1, CB2 and GPR55 receptors are implicated in the pathophysiology of diabetes type 2 (Jenkin et al., 2014; Jourdan et al., 2014; Troy-Fioramonti et al., 2014).
Functional gastrointestinal inflammation
A study in mice showed that GPR55 is involved in neurogenic gut contractions (Ross et al., 2012)
In rats, blocking GPR55 signaling reduced algesia suggesting GPR55 is a target for pain control (Deliu et al., 2015).
CBD and CBG do not function through classical CB receptors and none of the phytocannabinoids depended on TRPV1 for their effect (in contrast to endocannabinoid function below), but PPARγ and GPR55 may be involved in the effect of cannainoids in psoriasis (Wilkinson and Williamson, 2007).
Bakali, E., Elliott, R.A., Taylor, A.H., Lambert, D.G., Willets, J.M., and Tincello, D.G. (2014).Human urothelial cell lines as potential models for studying cannabinoid and excitatory receptor interactions in the urinary bladder. Naunyn. Schmiedebergs Arch. Pharmacol. 387, 581–589.
Bouron, A. (2018). Phyto and endocannabinoids exert complex actions on calcium and zinc signaling in mouse cortical neurons. Biochem. Pharmacol. 152, 244–251.
Calatozzolo, C., Salmaggi, A., Pollo, B., Sciacca, F.L., Lorenzetti, M., Franzini, A., Boiardi, A., Broggi, G., and Marras, C. (2007). Expression of cannabinoid receptors and neurotrophins in human gliomas. Neurol. Sci. Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol. 28, 304–310.
Deliu, E., Sperow, M., Console-Bram, L., Carter, R.L., Tilley, D.G., Kalamarides, D.J., Kirby, L.G., Brailoiu, G.C., Brailoiu, E., Benamar, K., et al. (2015). The Lysophosphatidylinositol Receptor GPR55 Modulates pain Perception in the Periaqueduactal Grey. Mol. Pharmacol.
Ellert-Miklaszewska, A., Grajkowska, W., Gabrusiewicz, K., Kaminska, B., and Konarska, L. (2007). Distinctive pattern of cannabinoid receptor type II (CB2) expression in adult and pediatric brain tumors. Brain Res. 1137, 161–169.
Jenkin, K.A., McAinch, A.J., Zhang, Y., Kelly, D.J., and Hryciw, D.H. (2014). Elevated CB1 and GPR55 receptor expression in proximal tubule cells and whole kidney exposed to diabetic conditions. Clin. Exp. Pharmacol. Physiol.
Jourdan, T., Szanda, G., Rosenberg, A.Z., Tam, J., Earley, B.J., Godlewski, G., Cinar, R., Liu, Z., Liu, J., Ju, C., et al. (2014). Overactive cannabinoid 1 receptor in podocytes drives type 2 diabetic nephropathy. Proc. Natl. Acad. Sci. U. S. A. 111, E5420–E5428.
Kerr, D.M., Downey, L., Conboy, M., Finn, D.P., and Roche, M. (2013). Alterations in the endocannabinoid system in the rat valproic acid model of autism. Behav. Brain Res. 249, 124–132
Sánchez, C., de Ceballos, M.L., Gomez del Pulgar, T., Rueda, D., Corbacho, C., Velasco, G., Galve-Roperh, I., Huffman, J.W., Ramón y Cajal, S., and Guzmán, M. (2001). Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. cancer Res. 61, 5784–5789.
Shi, Q.-X., Yang, L.-K., Shi, W.-L., Wang, L., Zhou, S.-M., Guan, S.-Y., … Yang, Q. (2017). The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress. Molecular Brain, 10(1), 38. https://doi.org/10.1186/s13041-017-0318-7
Troy-Fioramonti, S., Demizieux, L., Gresti, J., Muller, T., Vergès, B., and Degrace, P. (2014). Acute Activation of cannabinoid Receptors by Anandamide Reduces Gastro-Intestinal Motility and Improves Postprandial Glycemia in Mice. diabetes.
Wilkinson, J.D., and Williamson, E.M. (2007). cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of Psoriasis. J. Dermatol. Sci. 45, 87–92.