Compartmentalization of GPCR signaling is an emerging topic that highlights the physiological relevance of spatial bias in signaling. The parathyroid hormone (PTH) type 1 receptor (PTH₁R) was the first GPCR described to signal via heterotrimeric G-protein and cAMP from endosomes after β-arrestin mediated internalization, challenging the canonical GPCR signaling model which established that signaling is terminated by receptor internalization. More than a decade later, many other GPCRs have been shown to signal from endosomes via cAMP, and recent studies have proposed that location of cAMP generation impacts physiological outcomes of GPCR signaling. Here, we review the extensive literature regarding PTH₁R endosomal signaling via cAMP, the mechanisms that regulate endosomal generation of cAMP, and the implications of spatial bias in PTH₁R physiological functions.

GPCR 信号传导的区室化是一个新兴主题，强调信号传导中空间偏差的生理相关性。甲状旁腺激素 (PTH) 1 型受体 (PTH ₁ R) 是第一个被描述为在 β-arrestin 介导的内化后通过异三聚体 G 蛋白和来自内体的 cAMP 发出信号的 GPCR，挑战了经典的 GPCR 信号传导模型，该模型确立了信号传导通过以下途径终止：受体内化。十多年后，许多其他 GPCR 已被证明可以通过 cAMP 从内体发出信号，并且最近的研究提出 cAMP 生成的位置会影响 GPCR 信号传导的生理结果。_{在这里，我们回顾了有关通过 cAMP 的 PTH 1} R 内体信号传导、调节 cAMP 内体生成的机制以及空间偏差对 PTH ₁ R 生理功能的影响的大量文献。