title: [Development and repair of NSAIDs-induced small intestinal lesions: relation to COX isozymes and EP receptor subtypes].
abstract: Intestinal ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2, and inhibition of COX-1 up-regulates COX-2 expression and PGs produced by COX-2 counteract the deleterious influences of the COX-1 inhibition. These lesions are prevented by PGE2 mediated by EP3/EP4 receptors and functionally associated with stimulation of mucus secretion, inhibition of intestinal contraction or enterobacterial invasion, and down-regulation of cytokine expression. COX/PGE2 also plays an important role in the healing of these lesions, but the COX isozyme responsible for PG production differs depending on the stage of healing; COX-2 in the early stage and COX-1 in the late stage, and the healing-promoting action of PGE2 is mediated by the activation of EP4 receptors, through enhancing angiogenesis via an increase in VEGF expression.
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology, Kyoto Pharmaceutical University.
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D006801:Humans; D007410:Intestinal Diseases / Q000139:chemically induced; D007421:Intestine, Small / Q000187:drug effects*; D018078:Receptors, Prostaglandin E / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018078:Receptors, Prostaglandin E; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2