Abstract

 Introduction

 Materials
& Methods

 Results

 Discussion
& Conclusions

 References
 
 
 
 

Discussion
Board

Prostaglandins (PG) are mediators of numerous physiological and pathophysiological processes and are produced from arachidonic acid through the activity of two isoforms of cyclo-oxygenase (COX). COX-1 is constitutively expressed; COX-2 is induced in inflammation. PGE₂ stimulates chloride and water secretion in the intestine and acts as the final mediator of many secretagogues. However, the isoform of COX responsible for PGE₂ synthesis in the intestinal has not been described.  According to current dogma, PGE2 synthesis in uninflamed intestine occurs via COX-1, whereas PGE₂ synthesis in inflamed gut may be dependent upon both COX-1 and COX-2.  However, our preliminary evidence from the mouse shows that normal, uninflamed colon constitutively expresses both COX-1 and COX-2 mRNA, suggesting that COX inhibitors of varying selectivity for a given COX isoform may differentially affect secretion. In electrolyte transport studies conducted in vitro, we have shown that the PG-dependent secretory responses to bradykinin and arachidonic acid are inhibited by piroxicam, a non-selective inhibitor of both COX isoforms.  Interestingly, in normal tissue, the secretory response to these PG-dependent secretagogues is partially inhibited by COX-2 selective inhibitors such as SC58125 and NS-398, at concentrations which do not affect COX-1 activity.  These data challenge the dogma that physiological PG-dependent secretion is exclusively COX-1 dependent, and suggest that selective COX-2 inhibitors may alter normal secretory processes. 

Presentation Number SAmacnaughton0399
Keywords: cyclooxygenase, prostaglandins, electrolyte transport, intestine, epithelium

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