Several 7TM receptors have been cloned but theirendogenous ligands are unknown; these have been termed orphan receptors. However, recent research has identified certain pharmacological targets that could be investigated to find, for example, new potential cannabinoid receptors or channels [, , ]. GPR18 [, ], GPR55 [, ], GPR119 []show little structural similarity to CB1 and CB2 receptors, but they respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands []. However, because they do not fulfill all of the cannabinoid receptor criteria defined by IUPHAR, the classification of these proteins remains a contentious issue due to conflicting pharmacological results. As a result, they remain classified as putative endogenous agonists by IUPHAR [].This entry represents G protein-coupled receptor 55. It is thought to play a role in bone physiology by regulating osteoclast number and function [].
Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. However, recent research has identified certain pharmacological targets that could be investigated to find, for example, new potential cannabinoid receptors or channels [, , ]. GPR18 [, ], GPR55 [, ], GPR119 []show little structural similarity to CB1 and CB2 receptors, but they respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands []. However, because they do not fulfill all of the cannabinoid receptor criteria defined by IUPHAR, the classification of these proteins remains a contentious issue due to conflicting pharmacological results. As a result, they remain classified as putative endogenous agonists by IUPHAR [].This entry represents G protein-coupled receptor 18, also known as N-arachidonyl glycine receptor. It has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors [, , , ]. Recent research also supports the hypothesis that GPR18 is the abnormal cannabidiol receptor and N-arachidonoyl glycine, the endogenous lipid metabolite of anandamide, initiates directed microglial migration in the CNS through activation of GPR18 []. However, the pairing of GPR18 with N-arachidonoylglycine (NAGly) and tetrahydrocannabinol (THC) was not reproduced in two studies based on beta-arrestin assays [, ]. So, until further research allows a more definitive decision the function and nomenclature GPR18 is still being debated [, ].
Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. However, recent research has identified certain pharmacological targets that could be investigated to find, for example, new potential cannabinoid receptors or channels [, , ]. GPR18 [, ], GPR55 [, ], GPR119 []show little structural similarity to CB1 and CB2 receptors, but they respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands []. However, because they do not fulfill all of the cannabinoid receptor criteria defined by IUPHAR, the classification of these proteins remains a contentious issue due to conflicting pharmacological results. As a result, they remain classified as putative endogenous agonists by IUPHAR [].This entry represents glucose-dependent insulinotropic receptor, also known as G protein-coupled receptor 119. It is expressed predominantly in the pancreas and gastrointestinal tract in rodents and humans, as well as in the brain in rodents []. It has been shown to be involved in the control of glucose-dependent insulin release and glucagon-like peptide 1 release, respectively [, ], which caused a reduction in food intake and body weight gain in rats []. GPR119 has also been shown to regulate incretin and insulin hormone secretion [, , ], behaving as a glucose-dependent insulinotropic receptor. As a result, new drugs acting on the receptor have been suggested as novel treatments for obesity and diabetes [, , ]. Although GPR119 is phylogenetically related to cannabinoid receptors, only fatty acid amides interact with GPR119 [, , , ]. The potency order is N-oleoyl dopamine >oleoyl ethanolamide >palmitoyl ethanolamide >anandamide [, ]. However, because only N-oleoyl dopamine and oleoyl ethanolamide have reasonably high (low micromolar) affinity for GPR119, and because neither of these lipids interacts with CB1 or CB2 receptors, GPR119 cannot currently be viewed as a cannabinoid receptor [].
