Cannabinoid receptor 1–Cannabinoid receptor 2 heteroreceptor complex (CB1R-CB2R heteromer)

The Cannabinoid receptor 1–Cannabinoid receptor 2 (CB1R-CB2R) heteroreceptor complex is a functional unit formed by the physical association of two distinct G protein-coupled receptors (Callén et al., 2012, J Biol Chem). While CB1R is primarily expressed in the central nervous system and CB2R in the immune system, their co-expression and heteromerization occur in specific contexts, such as in activated microglia during neuroinflammation (Navarro et al., 2018, Front Pharmacol). This heteromerization results in novel pharmacological properties, including cross-antagonism, where an antagonist for one receptor can block the signaling of the other (Sierra et al., 2015, CNS Neurol Disord Drug Targets). These complexes are significant therapeutic targets because they allow for more precise modulation of the endocannabinoid system, potentially reducing the psychotropic side effects associated with pure CB1R activation. Research indicates their involvement in neurodegenerative conditions like Parkinson's disease and various inflammatory states, making them candidates for drug development using bivalent or allosteric ligands (Blasco-Benito et al., 2018, Br J Cancer).

Other names

CB1-CB2 heteromerCB1-CB2 receptor complexCNR1-CNR2 heteromerCannabinoid CB1-CB2 receptor heteromer

Allosteric interaction between protomers leading to cross-antagonism and biased signaling where the activation of one receptor modulates the signaling profile of the partner receptor.