Functions Studies using animals genetically engineered to lack EP2 and supplemented by studies examining the actions of EP2 receptor antagonists and agonists in animals as well as animal and human tissues indicate that this receptor serves various functions. Eye When applied topically into the eyes of rodents, cats, rhesus monkeys, and humans PGE2 acts, apparently acting at least in part through EP2, decreases intraocular pressure by stimulating increases in the drainage of aqueous humor through the uveoskceral pathway, the principal aqueous humor outflow pathway in the eye. Reproduction Female mice engineered to lack a functional Pgter2 gene show a modest reduction in ovulation and more severely impaired capacity for Fertilisation. Studies suggest that this impaired fertilization reflects the loss of EP2 functions in stimulating cumulus cells clusters which surround oocytes to: a) form the CCL7 chemokine which serves as a chemoattractant that guides sperm cells to oocytes and b) disassemble the extracellular matrix which in turn allows sperm cells to penetrate to the oocyte. These data allow that an EP2 receptor antagonist may be a suitable candidate as a contraceptive for women. Inflammation and allergy Activation of EP2 contributes to regulating B cell immunoglobulin class switching, maturation of T lymphocyte CD4−CD8− cells to CD4+CD8+ cells, and the function of Antigen-presenting cells, particularly Dendritic cells. EP thereby contributes to the development of inflammation in rodent models of certain types of experimentally-induced joint and paw inflammation and the neurotoxic effects of endotoxin. However, EP2 activation also has anti-inflammatory actions on pro-inflammatory cells (e.g. neutrophils, monocytes, macrophages, dendritic cells, NK cells, TH1 cells, TH2 cells, and fibroblasts in various tissues and on microglia cells in the central nervous system). These actions suppress certain forms of inflammation such NMDA receptor-related neurotoxicity and the rodent model of Bleomycin-induced pulmonary fibrosis. EP2 activation also inhibits the phagocytosis and killing of pathogens by alveolar macrophages; these effects may serve an anti-inflammatory role but reduce host defense against these pathogens. Activation of EP2 also influences allergic inflammatory reactions. It dilates airways (bronchodilation) contracted by the allergic mediator, histamine; inhibits Immunoglobulin E-activated mast cells from releasing histamine and leukotrienes (viz., LTC4, LTD4, and LTE4), all of which have bronchoconstricting and otherwise pro-allergic actions; inhibits pro-allergic eosinophil apoptosis, chemotaxis, and release of pro-allergic granule contents; and reduces release of the pro-allergic cytokines Interleukin 5, Interleukin 4, and interleukin 13 from human blood mononuclear cells. Cardiovascular EP2 receptor-deficient mice develop mild