are relatively resistant to being metabolically degraded. They are in development as drugs for the potential treatment of stomach ulcers in humans. Inhibiting ligands Numerous synthetic compounds have been found to be highly selective in binding to but not stimulating EP3. These Receptor antagonist DG-O41, L798,106, and ONO-AE3-240, block EP3 from responding to PGE2 or other agonists of this receptor, including Sulprostone, ONO-AE-248 and TEI-3356. They are in development primarily as anti-thrombotics, i.e. drugs to treat pathological blood clotting in humans. Mechanism of cell activation EP3 is classified as an inhibitory type of prostanoid receptor based on its ability, upon activation, to inhibit the activation of adenylyl cyclase stimulated by relaxant types of prostanoid receptors viz., prostaglandin DP, E2, and E4 receptors (see Prostaglandin receptors). When initially bound to PGE2 or other of its agonists, it mobilizes G proteins containing various types of G proteins, depending upon the particular EP3 isoform: EP3α and EP3β isoforms activate Gi alpha subunit (i.e. Gαi)-G beta-gamma complexes (i.e. Gαi)-Gβγ) complexes) as well as Gα12-Gβγ complexes while the EP3γ isoform activates in addition to and the Gαi- Gβγ complexes Gαi- Gβγ complexes. (G protein linkages for the other EP3 isoforms have not been defined.) In consequence, complexes dissociate into Gαi, Gα12, Gs and Gβγ components which proceed to activate cell signaling pathways that lead functional responses viz., pathways that activate phospholipase C to convert cellular phospholipids to diacylglycerol which promotes the activation of certain isoforms of protein kinase C, pathways that elevated cellular cytosolic Ca2+ which thereby regulate Ca2+-sensitive cell signaling molecules, and pathways that inhibit adenylyl cyclase which thereby lowers cellular levels of cyclic adenosine monophosphate (cAMP) to reduce the activity of cAMP-dependent signaling molecules. Functions Studies using animals genetically engineered to lack EP3 and supplemented by studies examining the actions of EP3 receptor antagonists and agonists in animals as well as animal and human tissues indicate that this receptor serves various functions. However, an EP3 receptor function found in these studies does not necessarily indicate that in does do in humans. For example, EP3 receptor activation promotes duodenal secretion in mice; this function is mediated by EP4 receptor activation in humans. EP receptor functions can vary with species and most of the functional studies cited here have not translated their animal and tissue models to humans. Digestive system The secretion of (bicarbonate anion) from Brunner's glands of the duodenum serves to neutralize the