Development and repair of NSAIDs-induced small intestinal lesions: relation to COX isozymes and EP receptor subtypes
Takeuchi, K.
Nihon Rinsho. Japanese Journal of Clinical Medicine 69(6): 1123-1128
2011
ISSN/ISBN: 0047-1852 PMID: 21688639 Document Number: 653624
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.