Year: 1996
Type: article
Abstract: Prostaglandins (PGs) are synthesized via cyclooxigenase pathway from arachidonic acid by cells responding to various physiological or pathological stimuli .They act as l ocal hormones by binding to specific receptors on plasma membranes, coupled to a variety of G proteins.G proteins in turn activate intracellular signal transduction netw ork s initiating with adenylate cyclase activation and inhibition, and phosphoinositide-Ca2+ mobilization.PG receptors characteri zed pharmacologically using several bioassay systems and biochentically using radioacti ve specific ligands .The studies show that PGs crossreact with one receptor, spggesting structural sintilarity of the receptors.Therefore, it i s required to perform eDNA cloning for PG receptors and their expression in mammalian cells, and to characteri ze their molecular structures and functions.We have recently cloned five basic PG receptors; DP, EP, FP, IP and TP, and four EP subtypes; EPI, 2, 3, 4, and three EP3 iso form s; a , ~y, of mice.EP receptors are coupled to multiple signal pathways via distinct G proteins.EP3 isoforms differ only C-terntinu s peptide, indicating a conformational domain to regulate the selectivity of G protein coupling.On the other hand, interaction of Arg residue in the 7th TM with the carboxylic acid of PGE2 functi on in the Gs and Gq activation but not Gi acti vation, indicating multiple conformation of the receptor coupled to multi ple G proteins.The mRNAs were expressed in distinct cellul ar distribution in the kidney and the mucus epitheli al cells or smooth muscle cells of the stomach, small and large intesti nes.Such functional elucidation will facilitate the development of subtype-specific and signal pathwayspeci fi c agonist and antagonists for potential therapeutic uses.
Institution: Kyoto University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W3101573620