Regulación alostérica en el heteroreceptor oxitocina - cannabinoide CB1: una nueva estrategia terapéutica para el tratamiento de trastornos de ansiedad

Abstract

G-protein coupled membrane receptors (GPCRs) can establish interactions between two or more receptors. It has been described that allosteric regulation may exist in these receptor-receptor interactions. Therefore, the formation of these complex structures and the regulation among the protomers involved in the protein-protein interaction represent therapeutic targets for anxiety, fear, and depression treatments. HeLa cells that transiently express oxytocin (OxTR) and cannabinoid CB1R (CB1R) receptors are a worthy study model of protein-protein interactions. The results indicate that these receptors co-localize in specific areas of the cell membrane, which could suggest the formation of the OxTR / CB1R heteroreceptor. In addition, the administration of anandamide, a specific CB1R agonist, induces the internalization of OxTR, which would indicate a positive allosteric regulation between OxTR and CB1R. The data obtained represent the first evidence of the OxTR / CB1R heteroreceptor formation and the nature of the allosteric regulation that takes place in this complex structure. Therefore, this heteromer could establish a target for the design of new drugs for the treatment of anxiety disorders.