Unique/Rapid Feedback Mechanisms of PGD2 and PGE2 as Local/Short-Lived Autacoids; Implications of Biased Activities by Their Metabolites.

Prostanoids are involved in various physiological/pathophysiological functions, such as inflammation. Since persistent inflammation may cause chronic symptoms, their activation is very short and needs to be properly terminated. Due to structural similarities, some prostanoids and their metabolites may have ability to activate noncognate prostanoid receptors as biased agonists and/or blockers. However, the physiological roles of these biased activities remain unclear. This review mainly focused on prostaglandin (PG) E2 and PGD2 as well as their metabolites, and hypothesized that the physiological roles of their biased activities may be novel nongenomic immediate feedback systems strictly confined to local areas as autacoids. These nongenomic feedback systems completely differ from the genomic feedback systems used by endocrine hormones. Therefore, the biased activities of prostanoids may be newly defined and/or re-acknowledged as unique, rapid, and fine-tuned translation/transcription-free feedback systems which may be responsible for the roles of prostanoids in maintaining homeostasis as rapid-acting local-mediators, autacoids.