Dopamine receptors: Potential therapeutic targets for ischemia-reperfusion injury: A review

As one of the most extensively studied neurotransmitters in the central nervous system, dopamine exerts its biological effects primarily through its receptors. Cryo-electron microscopy has elucidated the high-resolution architecture of dopamine receptors, in parallel, their biological properties, including protein-protein interactions, oligomerization, biased signaling, and endocytosis, have been extensively characterized. In recent years, growing evidence underscores a critical role for dopamine receptors in ischemia-reperfusion (I/R) injury. These receptors are not only widely distributed in the brain but also present in vital organs such as the heart and kidneys, where they exert protective regulatory effects through selective activation or inhibition under I/R stress. The underlying mechanisms involve enhancing neuroplasticity, maintaining the integrity of blood-brain barrier, inhibiting oxidative stress, and exerting anti-apoptotic effects, thereby providing comprehensive multi-organ protection. Pharmacological interventions targeting dopamine receptors have demonstrated significant therapeutic potential in I/R injury. Compounds with high binding affinity, effectiveness and safety, such as piribedil, tadalafil, salvianolic acid A, PD168077, and bromocriptine, have emerged as promising candidates for clinical translation. Future advancements in multi-omics and imaging technologies will enable a deeper understanding of mechanisms in dopamine receptor-mediated I/R injury. Concurrently, cutting-edge methods like artificial intelligence offer new perspectives and tools for rational design of drugs targeting these receptors for I/R injury treatment. In-depth exploration of dopamine receptors provides a critical entry point for elucidating the complex pathophysiological mechanisms of I/R injury, while also laying a solid theoretical foundation for development of novel and effective therapeutic strategies.