Exploiting D ₂ receptor ??arrestin2?biased signalling to suppress tumour growth of pituitary adenomas

Background and Purpose Dopamine agonists targeting D2 receptor have been used for decades in treating pituitary adenomas. There has little clear evidence implicating the canonical G protein signalling as mechanism by which suppresses growth of tumours. We hypothesize that ?-arrestin2-dependent is molecular dictating inhibitory effects on tumour growth. Experimental Approach The involvement ?-arrestin2 bromocriptine-mediated suppression rat MMQ GH3 cells was assessed. anti-growth effect a ?-arrestin2-biased agonist, UNC9994, tested cultured cells, tumour-bearing nude mice primary human also analysed using protein-biased MLS1547, G?? inhibitor, gallein, vitro. Key Results but not pathways mediated suppressive bromocriptine UNC9994 inhibited cell vitro vivo. function obtained inducing intracellular reactive oxygen species generation through downregulating mitochondrial complex I subunit NDUFA1. G?i/o via were cell-type-dependent. Conclusion Implications Given very low expression proteins tumours complexity responses to pathways, our study reveals ligand may be more promising choice treat with improved therapeutic selectivity.