Advances in the Physiology of GPR55 in the Central Nervous System.

The G protein-coupled receptor 55 (GPR55) is a mammalian orphan receptor whose functions in the central nervous system (CNS) have been scarcely elucidated. Several endogenous lipids (cannabinoids and non-cannabinoid) may activate GPR55; these facts have raised a discussion about its nature as a putative cannabinoid receptor. Lysophosphatidylinositol (LPI) is a non-endocannabinoid lipid with activity as a full and potent agonist of GPR55. Beyond this controversy, it is known the endocannabinoid system and GPR55 are highly related both in anatomical localization and function. Peripherally, GPR55 participates in bone physiology, cardiovascular function, intestinal activity, pain regulation among others. In the brain, GPR55 high expression has been reported in the striatum and frontal cortex. Striatal GPR55 seems to participate in the formation of procedural memories in rats, but no information has been reported so far about its function in the cortex. However, GPR55 seems to play a role during axonal navigation and fine-tuning of synapses in other brain areas. GPR55 mRNA is expressed in the hippocampus, hypothalamus, frontal cortex and cerebellum, but only some speculative information about its function in these regions has been suggested. Therefore, the purpose of this review is to discuss the experimental information available about GPR55 function in the central nervous system.