Prostanoids are the cyclooxygenase metabolites of arachidonic acid and include prostaglandin (PG) D(2), PGE(2), PGF(2alpha), PGI(2), and thromboxne A(2). They are synthesized and released upon cell stimulation and act on cells in the vicinity of their synthesis to exert their actions. Receptors mediating the actions of prostanoids were recently identified and cloned. They are G protein-coupled receptors with seven transmembrane domains. There are eight types and subtypes of prostanoid receptors that are encoded by different genes but as a whole constitute a subfamily in the superfamily of the rhodopsin-type receptors. Each of the receptors was expressed in cultured cells, and its ligand-binding properties and signal transduction pathways were characterized. Moreover, domains and amino acid residues conferring the specificities of ligand binding and signal transduction are being clarified. Information also is accumulating as to the distribution of these receptors in the body. It is also becoming clear for some types of receptors how expression of their genes is regulated. Furthermore, the gene for each of the eight types of prostanoid receptor has been disrupted, and mice deficient in each type of receptor are being examined to identify and assess the roles played by each receptor under various physiological and pathophysiological conditions. In this article, we summarize these findings and attempt to give an overview of the current status of research on the prostanoid receptors.

Diabetes, a disease in which the body does not produce or use insulin properly, is a serious global health problem. Gut polypeptides secreted in response to food intake, such as glucagon-like peptide-1 (GLP-1), are potent incretin hormones that enhance the glucose-dependent secretion of insulin from pancreatic beta cells. Free fatty acids (FFAs) provide an important energy source and also act as signaling molecules in various cellular processes, including the secretion of gut incretin peptides. Here we show that a G-protein-coupled receptor, GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain FFAs. Furthermore, we show that the stimulation of GPR120 by FFAs promotes the secretion of GLP-1 in vitro and in vivo, and increases circulating insulin. Because GLP-1 is the most potent insulinotropic incretin, our results indicate that GPR120-mediated GLP-1 secretion induced by dietary FFAs is important in the treatment of diabetes.

Prostaglandin (PG) E 2 exerts its actions by acting on a group of G-protein-coupled receptors (GPCRs). There are four GPCRs responding to PGE 2 designated subtypes EP1, EP2, EP3, and EP4 and multiple splicing isoforms of the subtype EP3. The EP subtypes exhibit differences in signal transduction, tissue localization, and regulation of expression. This molecular and biochemical heterogeneity of PGE receptors leads to PGE 2 being the most versatile prostanoid. Studies on knock-out mice deficient in each EP subtype have defined PGE 2 actions mediated by each subtype and identified the role each EP subtype plays in various physiological and pathophysiological responses. Here we review recent advances in PGE receptor research. Prostanoids including various prostaglandins (PGs)2 and thromboxanes (TXs) are cyclooxygenase (COX) metabolites of C20-unsaturated fatty acids such as arachidonic acid. These substances are synthesized in response to various stimuli in a variety of cells, released immediately after synthesis, and act in the vicinity of their synthesis to maintain local homeostasis (1). Among prostanoids, the E type PGs, particularly PGE 2 derived from arachidonic acid, is most widely produced in the body, most widely found in animal species, and exhibits the most versatile actions. Receptors mediating prostanoid actions were characterized first by pharmacological analysis, which indicated the presence of one receptor each, named DP, FP, IP, and TP, for PGs of the D, F, and I types and TXA, respectively, and four different receptors designated EP1, EP2, EP3, and EP4 for the E type PGs (reviewed in Refs. 2 and 3). Molecular identification of these receptors was achieved by their cDNA cloning, which revealed that the prostanoid receptors are G-proteincoupled receptors (GPCRs) and that there is indeed a family of eight GPCRs that correspond to the pharmacologically defined receptors. In addition, a recent study revealed the presence of the ninth prostanoid receptor that belongs not to the prostanoid receptor family described above but to the chemoattractant receptor family (4). This receptor called CRTH2 or DP2 is expressed in Th2 cells and eosinophils and mediates some of the PGD 2 actions on these cells such as chemotaxis. cDNA cloning also revealed the presence of several splicing variants for EP3. Thus, there are four GPCRs designated subtypes EP1, EP2, EP3, and EP4 and EP3 variants mediating PGE 2 actions. Subsequent analysis has revealed distinct biochemical properties and tissue and cellular localization of each EP subtype. The cloned EP subtypes have also been used in the development of compounds specific to each subtype. Biochemical Properties of PGE Receptor Subtypes and IsoformsMolecular Structures- Fig. 1 shows an alignment of the primary amino acid sequences of the mouse EP1, EP2, and EP4 and three isoforms of mouse EP3 receptors. The mouse EP1, EP2, EP3 (EP3␣), and EP4 receptors consist of 405, 362, 366, and 513 amino acids, respectively. EP4 has the longest intracellular C terminus and a relatively l...

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (http://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein‐coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.