TY - JOUR
T1 - Introduction to eicosanoids and the gastroenteric tract
AU - Dubois, R. N.
AU - Eberhart, C. E.
AU - Williams, C. S.
PY - 1996
Y1 - 1996
N2 - Eicosanoids are produced throughout the gastrointestinal tract and are significant mediators of physiologic and pathophysiologic processes. Understanding the precise role(s) of specific eicosanoid metabolites remains a significant challenge, but has led to the development of new pharmacologic strategies for treating NSAID-induced, gastroenteropathy and IBD. Given the complex array of arachidonic acid metabolites, the development of more specific and potent inhibitors of these cyclooxygenase isoforms is important for future studies and possible therapeutic applications. Mice have been prepared that lack expression of COX-1 or COX-2. Once these animals have been carefully evaluated, understanding of the role of various pathways of eicosanoid formation in gastrointestinal function, development, and epithelial growth regulation might be improved. Considerable progress has been made in the understanding of arachidonic acid metabolism and in eicosanoid receptor biology. The identification and characterization of an inducible cyclooxygenase isoform has led to important studies evaluating the role of this enzyme in inflammation, neoplasia, and NSAID-induced gastrointestinal injury. The demonstration that COX-2 overexpression in intestinal epithelial cells leads to specific phenotypic changes, such as increased adhesion and inhibition of apoptosis, indicates that this enzyme may alter the tumorigenic potential of epithelial cells and offers hope for the future development of improved chemopreventive agents.
AB - Eicosanoids are produced throughout the gastrointestinal tract and are significant mediators of physiologic and pathophysiologic processes. Understanding the precise role(s) of specific eicosanoid metabolites remains a significant challenge, but has led to the development of new pharmacologic strategies for treating NSAID-induced, gastroenteropathy and IBD. Given the complex array of arachidonic acid metabolites, the development of more specific and potent inhibitors of these cyclooxygenase isoforms is important for future studies and possible therapeutic applications. Mice have been prepared that lack expression of COX-1 or COX-2. Once these animals have been carefully evaluated, understanding of the role of various pathways of eicosanoid formation in gastrointestinal function, development, and epithelial growth regulation might be improved. Considerable progress has been made in the understanding of arachidonic acid metabolism and in eicosanoid receptor biology. The identification and characterization of an inducible cyclooxygenase isoform has led to important studies evaluating the role of this enzyme in inflammation, neoplasia, and NSAID-induced gastrointestinal injury. The demonstration that COX-2 overexpression in intestinal epithelial cells leads to specific phenotypic changes, such as increased adhesion and inhibition of apoptosis, indicates that this enzyme may alter the tumorigenic potential of epithelial cells and offers hope for the future development of improved chemopreventive agents.
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U2 - 10.1016/S0889-8553(05)70246-6
DO - 10.1016/S0889-8553(05)70246-6
M3 - Article
C2 - 9229572
AN - SCOPUS:0029939611
SN - 0889-8553
VL - 25
SP - 267
EP - 277
JO - Gastroenterology Clinics of North America
JF - Gastroenterology Clinics of North America
IS - 2
ER -