Department of Pharmacology for Life Sciences, Graduate School of Pharmaceutical Sciences & Graduate School of Biomedical Sciences, Tokushima University.
Biol Pharm Bull. 2022;45(6):684-690. doi: 10.1248/bpb.b21-01052.
Since the discovery of β-arrestin, a new concept/viewpoint has arisen in G-protein coupled receptor (GPCR)-mediated signaling. The Lock and Key concept of GPCR was previously recognized as basically a single- or mono-originated pathway activated from a single receptor. However, the new concept/viewpoint allows for many- or more-than-one-originated pathways activated from a single receptor; namely, biased activities. It is well-recognized that prostanoids exhibit preferences for their corresponding cognate receptors, while promiscuous cross-reactivities have also been reported among endogenous prostanoids and their receptor family. However, of particular interest, such cross-reactivities have led to reports of their physiologically significant roles. Thus, this review discusses and considers that the endogenous prostanoids are not showing random cross-reactivities but what are showing important physiological and pathological activities as biased ligands. Moreover, why and how the biased activities are evoked by endogenous structurally similar prostanoid ligands are discussed. Furthermore, when the biased activities of endogenous prostanoids first arose is also discussed and considered. These biased activities of endogenous prostanoids are also discussed from the perspective that they may provide many benefits and/or disadvantages for all living things, any-where on this planet, who/which are utilizing, had utilized, and will utilize the prostanoids and their receptor system, as a marked driving force for evolution.
自 β-arrestin 被发现以来，G 蛋白偶联受体（GPCR）介导的信号转导中出现了一个新概念/观点。以前，GPCR 的“锁钥”概念基本上被认为是一种单一或单起源的途径，由单个受体激活。然而，新的概念/观点允许来自单个受体的多起源或多于一种起源途径被激活；即，偏性活性。众所周知，前列腺素类化合物对其相应的同源受体表现出偏好，而内源性前列腺素类化合物及其受体家族之间也存在混杂的交叉反应性。然而，特别值得注意的是，这些交叉反应性导致了它们具有生理意义的作用的报道。因此，本综述讨论并认为，内源性前列腺素类化合物不是随机地表现出交叉反应性，而是作为偏性配体表现出重要的生理和病理活性。此外，还讨论了内源性结构相似的前列腺素类化合物如何以及为何诱发偏性活性。此外，还讨论了内源性前列腺素类化合物的偏性活性最初是如何出现的，并认为这可能是进化的一个显著驱动力，因为它们可能为这个星球上任何地方的所有生物提供许多好处和/或坏处，而这些生物正在利用、曾经利用过、并将利用前列腺素类化合物及其受体系统。
