GPR139, a vertebrate orphan receptor, is very closely related to GPR142, but they have different expression patterns in the brain and in other tissues [, ]. These receptors couple to inhibitory G proteins and activate phospholipase C. GPR142 is predominantly expressed in pancreatic beta-cells and plays an important role in mediating insulin secretion and maintaining glucose homeostasis, whereas GPR139 is expressed almost exclusively in the brain and is suggested to play a role in the control of locomotor activity []. Tryptophan and phenylalanine have been identified as putative endogenous ligands of GPR139 []. These orphan receptors are phylogenetically clustered with invertebrate FMRFamide receptors such as Drosophila melanogaster DrmFMRFa-R [].
