title: Role of the A(2B) receptor-adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats.
abstract: OBJECTIVE
  Adenosine A(2B) 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 A2B receptors in rat colon and their role in the control of cholinergic motility in the presence of bowel inflammation.
  
  
  METHODS
  Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS). Colonic A(2B) receptor expression and localization were examined by RT-PCR and immunofluorescence. The interaction between A(2B) receptors and adenosine deaminase was assayed by immunoprecipitation. The role of A(2B) receptors in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs).
  
  
  RESULTS
  A(2B) receptor mRNA was present in colon from both normal and DNBS-treated rats but levels were increased in the latter. A(2B) receptors were predominantly located in the neuromuscular layer, but, in the presence of colitis, were increased mainly in longitudinal muscle. Functionally, the A(2B) 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(2B) receptor agonist NECA decreased colonic cholinergic motility, with increased efficacy in inflamed LMP. Immunoprecipitation and functional tests revealed a link between A(2B) receptors and adenosine deaminase, which colocalize in the neuromuscular compartment.
  
  
  CONCLUSIONS
  Under normal conditions, endogenous adenosine modulates colonic motility via A2B receptors located in the neuromuscular compartment. In the presence of colitis, this inhibitory control is impaired due to a link between A2B receptors and adenosine deaminase, which catabolizes adenosine, thus preventing A(2B) receptor activation.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Antonioli
authors.forename: M
authors.initials: M
authors.lastname: Fornai
authors.forename: O
authors.initials: O
authors.lastname: Awwad
authors.forename: G
authors.initials: G
authors.lastname: Giustarini
authors.forename: C
authors.initials: C
authors.lastname: Pellegrini
authors.forename: M
authors.initials: M
authors.lastname: Tuccori
authors.forename: V
authors.initials: V
authors.lastname: Caputi
authors.forename: M
authors.initials: M
authors.lastname: Qesari
authors.forename: I
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: P
authors.initials: P
authors.lastname: Brun
authors.forename: M C
authors.initials: MC
authors.lastname: Giron
authors.forename: C
authors.initials: C
authors.lastname: Scarpignato
authors.forename: C
authors.initials: C
authors.lastname: Blandizzi
authors.forename: R
authors.initials: R
authors.lastname: Colucci
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000502:physiology*; D058892:Adenosine Deaminase Inhibitors / Q000494:pharmacology; D000818:Animals; D001557:Benzenesulfonates; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043704:Receptor, Adenosine A2B / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058892:Adenosine Deaminase Inhibitors; D001557:Benzenesulfonates; D043704:Receptor, Adenosine A2B; D014409:Tumor Necrosis Factor-alpha; C001073:2,4-dinitrobenzenesulfonic acid; C010192:9-(2-hydroxy-3-nonyl)adenine; D009195:Peroxidase; D000243:Adenosine Deaminase; D000225:Adenine
keywords: A2B receptor; adenosine; colitis; colonic neuromuscular contractions