Angiogenesis: a new physiological role for N‐arachidonoyl serine and GPR55?

N‐arachidonoyl serine (ARA‐S) is one of a number of acyl amino acids recently identified in mammalian tissues. It has been referred to as an endocannabinoid‐like lipid largely based on its structural similarities with the endocannabinoid, N‐arachidonoyl ethanolamide (anandamide). However, little is known about its potential physiological functions and receptor targets. In this issue of the British Journal of Pharmacology, Zhang and colleagues show that ARA‐S is a potent inducer of endothelial cell proliferation and migration, and angiogenesis in vitro. Furthermore, this pro‐angiogenic action is mediated, at least partly, by activation of the poorly characterized, G‐protein‐coupled GPR55 receptor. ARA‐S, via GPR55, increases phosphorylation of extracellular signal‐regulated kinases and Akt, and vascular endothelial growth factor signalling. These exciting findings highlight the endothelium as an endogenous target for ARA‐S and GPR55.