自从发现β-抑制蛋白以来,在G蛋白偶联受体(GPCR)介导的信号传导中出现了一个新的概念/观点。GPCR的Lock和Key概念以前基本上被认为是由单个受体激活的单个或单个起源的途径。然而,新的概念/观点允许从单个受体激活许多或多个起源的途径;即有偏见的活动。众所周知,前列腺素类表现出对其相应同源受体的偏好,虽然内源性前列腺素及其受体家族之间也有混杂交叉反应性的报道。然而,特别感兴趣的是,这种交叉反应导致了有关其生理上重要作用的报道。因此,这篇综述讨论并认为内源性前列腺素并没有表现出随机的交叉反应性,而是表现出重要的生理和病理活性作为偏向性配体。此外,讨论了内源性结构相似的前列腺素配体为何以及如何引起偏倚活性。此外,还讨论并考虑了内源性前列腺素的偏倚活性何时首次出现。内源性前列腺素的这些偏向活性也从它们可能为所有生物提供许多益处和/或缺点的角度进行了讨论。在这个星球上的任何地方,谁/谁在利用,已经利用,并将利用前列腺素和它们的受体系统,作为进化的显著驱动力。
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.