G protein-coupled receptors (GPCRs) regulate every aspect of kidney function by mediating the effects of various endogenous and exogenous substances. A key concept in GPCR function is biased signalling, whereby certain ligands may selectively activate specific pathways within the receptor’s signalling repertoire. For example, different agonists may induce biased signalling by stabilizing distinct active receptor conformations — a concept that is supported by advances in structural biology. However, the processes underlying functional selectivity in receptor signalling are extremely complex, involving differences in subcellular compartmentalization and signalling dynamics. Importantly, the molecular mechanisms of spatiotemporal bias, particularly its connection to ligand binding kinetics, have been detailed for GPCRs critical to kidney function, such as the AT₁ angiotensin receptor (AT₁R), V₂ vasopressin receptor (V₂R) and the parathyroid hormone 1 receptor (PTH₁R). This expanding insight into the multifaceted nature of biased signalling paves the way for innovative strategies for targeting GPCR functions; the development of novel biased agonists may represent advanced pharmacotherapeutic approaches to the treatment of kidney diseases and related systemic conditions, such as hypertension, diabetes and heart failure.

G 蛋白偶联受体 (GPCR) 通过介导各种内源性和外源性物质的作用来调节肾功能的各个方面。 GPCR 功能的一个关键概念是偏向信号传导，即某些配体可以选择性地激活受体信号传导库中的特定途径。例如，不同的激动剂可能通过稳定不同的活性受体构象来诱导有偏差的信号传导——这一概念得到了结构生物学进展的支持。然而，受体信号传导功能选择性的过程极其复杂，涉及亚细胞区室化和信号传导动力学的差异。重要的是，时空偏差的分子机制，特别是其与配体结合动力学的联系，已针对对肾功能至关重要的 GPCR 进行了详细说明，例如 AT ₁血管紧张素受体 (AT ₁ R)、V ₂加压素受体 (V ₂ R) 和甲状旁腺激素 1 受体 (PTH ₁ R)。这种对偏向信号传导多方面性质的深入了解，为针对 GPCR 功能的创新策略铺平了道路；新型偏向激动剂的开发可能代表治疗肾脏疾病和相关全身性疾病（如高血压、糖尿病和心力衰竭）的先进药物治疗方法。