GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol.

GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol.
Acta Pharmacol Sin. 2018 Jun 25;:
Authors: Laun AS, Shrader SH, Brown KJ, Song ZH
Abstract
The G protein-coupled receptors 3, 6, and 12 (GPR3, GPR6, and GPR12) comprise a family of closely related orphan receptors with no confirmed endogenous ligands. These receptors are constitutively active and capable of signaling through G protein-mediated and non-G protein-mediated mechanisms. These orphan receptors have previously been reported to play important roles in many normal physiological functions and to be involved in a variety of pathological conditions. Although they are orphans, GPR3, GPR6, and GPR12 are phylogenetically most closely related to the cannabinoid receptors. Using β-arrestin2 recruitment and cAMP accumulation assays, we recently found that the nonpsychoactive phytocannabinoid cannabidiol (CBD) is an inverse agonist for GPR3, GPR6, and GPR12. This discovery highlights these orphan receptors as potential new molecular targets for CBD, provides novel mechanisms of action, and suggests new therapeutic uses of CBD for illnesses such as Alzheimer's disease, Parkinson's disease, cancer, and infertility. Furthermore, identification of CBD as a new inverse agonist for GPR3, GPR6, and GPR12 provides the initial chemical scaffolds upon which potent and efficacious agents acting on these receptors can be developed, with ...

Source: Acta Pharmacologica Sinica - June 25, 2018 Category: Drugs & Pharmacology Authors: Laun AS, Shrader SH, Brown KJ, Song ZH Tags: Acta Pharmacol Sin Source Type: research