G protein-coupled purinergic P2Y receptor oligomerization: Pharmacological changes and dynamic regulation

P2Y receptors (P2YRs) are a δ group of rhodopsin-like G protein-coupled receptors (GPCRs) with many essential functions in physiology and pathology, such as platelet aggregation, immune responses, neuroprotective effects, inflammation, and cellular proliferation. Thus, they are among the most researched therapeutic targets used for the clinical treatment of diseases (e.g., the antithrombotic drug clopidogrel and the dry eye treatment drug diquafosol). GPCRs transmit signals as dimers to increase the diversity of signalling pathways and pharmacological activities. Many studies have frequently confirmed dimerization between P2YRs and other GPCRs due to their functions in cardiovascular and cerebrovascular processes in vivo and in vitro. Recently, some P2YR dimers that dynamically balance physiological functions in the body were shown to be involved in effective signal transduction and exert pathological responses. In this review, we summarize the types, pharmacological changes, and active regulators of P2YR-related dimerization, and delineate new functions and pharmacological activities of P2YR-related dimers, which may be a novel direction to improve the effectiveness of medications.