Receptors for acylethanolamides—GPR55 and GPR119

Acylethanolamides are lipid substances widely distributed in the body, generated from a membrane phospholipid precursor, N-acylphosphatidylethanolamine (NAPE). The recent identification of arachidonoyl ethanolamide (anandamide or AEA) as an endogenous cannabinoid ligand has focused attention on acylethanolamides, which has further increased with the subsequent identification of related additional acylethanolamides with signaling function, such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Most of the biological functions of anandamide are mediated by the two G protein-coupled cannabinoid receptors identified to date, CB1 and CB2, with the transient receptor potential vanilloid-1 receptor being an additional potential target. There has been increasing pharmacological evidence for the existence of additional cannabinoid receptors, with the orphan G protein-coupled receptor GPR55 being the most actively scrutinized, and is one of the subjects of this review. The other receptor reviewed here is GPR119, which can recognize OEA and PEA. These two acylethanolamides, although structurally related to anandamide, do not interact with classical cannabinoid receptors. Instead, they have high affinity for the nuclear receptor PPARα, which is believed to mediate many of their biological effects.