title: Modulation of ocular inflammatory responses by EP1 receptors in mice.
abstract: The purpose of the study was to investigate the role of EP1 receptors in intraocular inflammation and to determine possible interplay between EP1, EP2 and EP4 receptors. The eyes of separate groups of EP1 receptor knockout and wild type mice were: 1) treated topically with prostaglandin E2 (PGE2) or the EP2 receptor selective agonist, butaprost; 2) given intravitreal injection of LPS; or 3) paracentesis performed. Another group of knockout mice were pretreated topically with an EP4 receptor selective antagonist prior to paracentesis or LPS treatment. Results demonstrated a significant increase (50% or more) in the protein levels of aqueous humor of the EP1 knockout mice in response to PGE2, paracentesis or LPS. The leukocyte infiltration in the aqueous humor of the knockout mice was 47% higher when compared with that in the wild type controls in response to LPS injection. No significant change was observed in the protein levels in response to butaprost. Pretreating the knockout mice with an EP4 receptor antagonist prior to paracentesis and LPS treatment substantially reduced the aqueous humor protein levels. Also, the leukocyte count in the aqueous humor of the knockout mice in response to LPS was reduced 4 fold after pretreatment with EP4 receptor antagonist when compared with the findings in knockout mice receiving LPS only. We concluded that EP1 receptor has no modulatory effect on EP2 receptors but there is definitely cross-talk between EP1 and EP4 receptors.
authors.affiliation: Department of Ophthalmology and Visual Science, University of Louisville, 301E Muhammad Ali Blvd, Louisville, KY 40202, USA. s0bisw04@gwise.louisville.edu
authors.forename: S
authors.initials: S
authors.lastname: Biswas
authors.forename: P
authors.initials: P
authors.lastname: Bhattacherjee
authors.forename: C A
authors.initials: CA
authors.lastname: Paterson
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D018916:Blood-Aqueous Barrier / Q000187:drug effects / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D005136:Eye Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019152:Paracentesis; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype
chemical_list: D005136:Eye Proteins; D008070:Lipopolysaccharides; C545636:Ptger1 protein, mouse; C545645:Ptger2 protein, mouse; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone