P2Y receptors (P2YRs), a δ group of rhodopsin-like G protein-coupled
receptors (GPCRs), have 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 for use in the
clinical treatment of diseases (e.g., clopidogrel, an antithrombotic
drug, and Prolacria, a treatment for dry eye). Over the past two
decades, GPCRs have been revealed to transmit signals as dimers to
increase the diversity of signalling pathways or 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 pharmacological effects. In this review, we summarize the
types, pharmacological changes, and active regulators of P2YR-related
dimerization. In summary, our review delineates that P2YR-related dimers
have new functions and pharmacological activities and maybe a novel
direction to improve the effectiveness of medications such as thrombotic
events associated with COVID-19.
Structure-Based Approaches to Ligands for G-Protein-Coupled Adenosine and P2Y Receptors, from Small Molecules to Nanoconjugates
