Prostanoid receptors are activated by the endogenous ligands prostaglandin (PG) D2, PGE2, PGF2α, PGH2, prostacyclin (PGI2) and thromboxane A2. Cyclooxygenase (COX) converts arachidonic acid to PGH2, from which the other prostaglandins are synthesized. Prostanoid receptors are a family of nine G-protein-coupled receptors that have distinct tissue distributions and actions.
An overview of Prostanoid Receptor
Prostanoids, the lipid mediator, are composed of prostaglandins and thromboxanes. The prostanoids are fabricated by arachidonic acid and include five major prostanoids, involved in multiple biological processes such as allergy, inflammation, and tumorigenesis. When the body is stimulated by various factors, some cells in the body can synthesize these substances and release them rapidly, acting on adjacent tissues or peripheral tissues in paracrine or autocrine to maintain homeostasis. Meanwhile, these prostanoids exert functions by activating prostanoid receptors.
Major types of Prostanoid Receptor
E-type prostanoid (EP) receptors are an important class of prostanoid receptor, termed EP1, EP2, EP3 and EP4. EP1 was the first reported EP receptor and was found in kidney and lung tissue at a low level. The human EP1 receptor is composed of 402 amino acids, sharing a sequence homology of 86% with the rat EP1 receptor. EP2 and EP4 have the similarities in pharmacology and functional coupling, mediating celluar signaling via adenylate cyclase activity. The EP3 receptor is reported to have various isoforms that differ in the amino acid sequence of the C-terminal region.
Agonists/antagonists of Prostanoid Receptor
It’s obvious that the development of potent and selective agonists and antagonists of EP receptor is required for the research in prostanoid biology. ONO-DI-004, a derivate of PGE, is selective EP1 receptor agonist with moderate affinity with the receptor. ONO-8711 is a competitive EP1 receptor antagonist, inhibiting the increase of cytosolic Ca2+ concentration. Recently, more selective and potent EP2 receptor antagonists have been synthesized, such as AH-6809, PF-04418948, TG6-129, and TG4-155. There are many agonists and antagonists against the EP3 receptors developed due to the huge amount of EP3 isoforms. Commercially available EP4 agonists and antagonists have emerged since 2000.
Prostanoid Receptor and diseases
Prostanoid receptors are demonstrated to be involved in pathophysiological processes in respiratory conditions and are related to chronic respiratory diseases like asthma. Therefore, targeting prostanoid receptors is an attractive way to perform researches on lung health.
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Lebender, L. F., Prünte, L., Rumzhum, N. N. & Ammit, A. J. Selectively targeting prostanoid E (EP) receptor-mediated cell signalling pathways: Implications for lung health and disease. Pulmonary Pharmacology & Therapeutics 49, 75-87 (2018).