A complex system of interacting mediators exists in the gastric mucosa to strengthen its resistance against injury. In this system @entity2918 play an important role. Prostaglandin biosynthesis is catalysed by the enzyme cyclooxygenase (COX), which exists in two isoforms, @entity9774 and @entity4665 . Initially the concept was developed that @entity9774 functions as housekeeping enzyme, whereas @entity4665 yields prostaglandins involved in pathophysiological reactions such as @entity32 . In the gastrointestinal tract, the maintenance of mucosal integrity was attributed exclusively to @entity9774 without a contribution of @entity4665 and ulcerogenic effects of non-steroidal anti-inflammatory drugs (NSAIDs) were believed to be the consequence of inhibition of @entity9774 . Recent findings, however, indicate that both @entity9774 and @entity4665 either alone or in concert contribute to @entity356 . Thus, in normal @entity35 gastric mucosa specific inhibition of @entity9774 does not elicit @entity3137 despite near-maximal suppression of gastric prostaglandin formation. When a selective @entity4665 inhibitor which is not ulcerogenic when given alone is added to the @entity9774 inhibitor, severe @entity1819 develops. In contrast to normal gastric mucosa which requires simultaneous inhibition of @entity9774 and @entity4665 for breakdown of mucosal resistance, in the acid-challenged @entity35 stomach inhibition of @entity9774 alone results in dose-dependent injury which is further increased by additional inhibition of @entity4665 enzyme activity or prevention of acid-induced up-regulation of @entity4665 expression by @entity619 . @entity4665 inhibitors do not damage the normal or acid-challenged gastric mucosa when given alone. However, when @entity842 formation is suppressed or afferent nerves are defunctionalized, specific inhibition of @entity4665 induces severe @entity1819 . @entity63 -reperfusion of the gastric artery is associated with up-regulation of @entity4665 but not @entity9774 mRNA. @entity4665 inhibitors or @entity619 augment @entity63 -reperfusion-induced @entity1819 up to four-fold, an effect abolished by concurrent administration of @entity6328 . Selective inhibition of @entity9774 is less effective. Furthermore, @entity4665 inhibitors antagonize the protective effect of a mild irritant or intragastric peptone perfusion in the @entity35 stomach, whereas the protection induced by chronic administration of endotoxin is mediated by @entity9774 . Finally, an important function of @entity4665 is the acceleration of @entity1066 . @entity4665 is up-regulated in chronic @entity2275 and inhibitors of @entity4665 impair the healing of @entity1066 to the same extent as non-selective NSAIDs. Taken together, these observations show that both COX isoenzymes are essential factors in @entity33 with specific contributions in various physiological and pathophysiological situations.

Role of cyclooxygenase isoforms in XXXX .

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity1819 :: ('MESH:D013272', 'Disease') :: ['gastric damage'] @entity63 :: ('MESH:D007511', 'Disease') :: ['Ischemia', 'ischemia'] @entity6328 :: ('MESH:D015064', 'Chemical') :: ['16,16-dimethyl-PGE(2)'] @entity1066 :: ('MESH:D014456', 'Disease') :: ['ulcer healing', 'ulcers'] @entity33 :: ('MESH:D052016', 'Disease') :: ['mucosal defence'] @entity2918 :: ('MESH:D011453', 'Chemical') :: ['prostaglandins'] @entity9774 :: ('26195(Tax:10116)', 'Gene') :: ['COX-1'] @entity619 :: ('MESH:D003907', 'Chemical') :: ['dexamethasone'] @entity3137 :: ('MESH:D009059', 'Disease') :: ['mucosal lesions'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity4665 :: ('26198(Tax:10116)', 'Gene') :: ['COX-2'] @entity356 :: ('MESH:D013274', 'Disease') :: ['gastric mucosal defence'] @entity2275 :: ('MESH:D013276', 'Disease') :: ['gastric ulcers']
@entity356 :: (MESH:D013274,Disease) :: ['gastric mucosal defence']
