Emerging role of cyclooxygenase isoforms in the control of gastrointestinal neuromuscular functions

Since the discovery of two cyclooxygenase isoforms (COX-1, COX-2), efforts have been made to characterize the roles played by these enzymes in the regulation of physiological functions, as well as to explore their involvement in the pathophysiology of inflammatory disorders. In the digestive tract, the majority of evidence has been obtained at mucosal level, where both isoforms regulate various functions, and contribute to the development of inflammatory and neoplastic disorders. The role of COX isoforms in the gut neuromuscular compartment, where their expression has been detected in different species, is still unclear. However, the characterization of actions exerted by COX-derived prostanoids on gut motility has been under investigation for many years, and it is becoming increasingly appreciated that these mediators subserve complex regulatory patterns of COX on digestive motility. More recently, several studies have strengthened the concept that both COX-1 and COX-2 are involved in the modulation of gastrointestinal neuromuscular activity under normal conditions, and that changes in their regulatory activities occur in the presence of various digestive disorders, including inflammatory bowel diseases and postoperative ileus. Despite a large body of preclinical evidence, studies aimed at translating these findings into clinically relevant applications are needed, in an attempt to identify novel therapeutic approaches for treatment of gut disorders associated with motility alterations. This review illustrates and discusses current knowledge of the roles played by COX pathways in the regulation of gastrointestinal neuromuscular functions, both under normal conditions and in the presence of gut disorders.