Role of the A2B receptor–adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats. (March 2014)

• Record Type: Journal Article
• Authors: Antonioli, L; Fornai, M; Awwad, O; Giustarini, G; Pellegrini, C; Tuccori, M; Caputi, V; Qesari, M; Castagliuolo, I; Brun, P; Giron, M C; Scarpignato, C; Blandizzi, C; Colucci, R
• Is Part Of: British journal of pharmacology. Volume 171:Number 5(2014:Mar.)
• Page Start: 1314
• Page End: 1329
• Publication Date: 2014-03
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12539
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12539-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>Adenosine A<sub>2B</sub> receptors regulate several physiological enteric functions. However, their role in the pathophysiology of intestinal dysmotility associated with inflammation has not been elucidated. Hence, we investigated the expression of A<sub>2B</sub> receptors in rat colon and their role in the control of cholinergic motility in the presence of bowel inflammation.</p> </sec> <sec id="bph12539-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>Colitis was induced by 2, 4‐dinitrobenzenesulfonic acid (DNBS). Colonic A<sub>2B</sub> receptor expression and localization were examined by RT‐PCR and immunofluorescence. The interaction between A<sub>2B</sub> receptors and adenosine deaminase was assayed by immunoprecipitation. The role of A<sub>2B</sub> receptors in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs).</p> </sec> <sec id="bph12539-sec-0003" sec-type="section"> <title>Key Results</title> <p>A<sub>2B</sub> receptor mRNA was present in colon from both normal and DNBS‐treated rats but levels were increased in the latter. A<sub>2B</sub> receptors were predominantly located in the neuromuscular layer, but, in the presence of colitis, were increased mainly in longitudinal muscle. Functionally, the A<sub>2B</sub> receptor antagonist MRS 1754 enhanced both electrically‐evoked and carbachol‐induced cholinergic contractions in normal LMPs, but was less effective in inflamed tissues. The A<sub>2B</sub> receptor agonist NECA decreased colonic cholinergic motility, with increased efficacy in inflamed LMP. Immunoprecipitation and functional tests revealed a link between A<sub>2B</sub> receptors and adenosine deaminase, which colocalize in the neuromuscular compartment.</p> </sec> <sec id="bph12539-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>Under normal conditions, endogenous adenosine modulates colonic motility via A<sub>2B</sub> receptors located in the neuromuscular compartment. In the presence of colitis, this inhibitory control is impaired due to a link between A<sub>2B</sub> receptors and adenosine deaminase, which catabolizes adenosine, thus preventing A<sub>2B</sub> receptor activation.</p> </sec> </abstract>