Role of the A2B receptor-adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rat.

BACKGROUND AND PURPOSE: Adenosine A2B receptors (A2B R) regulate several physiological enteric functions. However, their role in the pathophysiology of intestinal dysmotility associated with inflammation is still less characterized. Our purpose was to investigate the A2B R expression in rat colon and their role in the control of cholinergic motility in the presence of bowel inflammation. EXPERIMENTAL APPROACH: Colitis was induced by 2,4-dinitrobenzenesulfonic acid. Colonic A2B R expression and localization were examined by RT-PCR and immunofluorescence. The interaction between A2B R and adenosine deaminase was assayed by immunoprecipitation. The role of A2B R in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMP). KEY RESULTS: RT-PCR revealed the presence of A2B R mRNA in normal colon, and its increased levels in inflamed tissues. Immunofluorescence displayed a predominant localization of A2B R in the colonic neuromuscular compartment, that was increased mainly at muscular level in the presence of colitis. Functionally, the A2B R antagonist MRS 1754, enhanced both electrically evoked and carbachol-induced cholinergic contractions in normal LMP, while it was less effective in inflamed tissues. The A2B R agonist NECA decreased the colonic cholinergic motility, with an increased efficacy in inflamed LMP. Immunoprecipitation and functional tests revealed a link between A2B R and adenosine deaminase that colocalize in the neuromuscular compartment. CONCLUSIONS AND IMPLICATIONS: Under normal conditions, endogenous adenosine modulates colonic motility via A2B R located in the neuromuscular compartment. In the presence of colitis, this inhibitory control is impaired, due to a link between A2B R and adenosine deaminase, which catabolises adenosine thus preventing A2B R activation.