title: A2a receptors mediate inhibitory effects of adenosine on colonic motility in the presence of experimental colitis.
abstract: BACKGROUND
  Adenosine regulates immunity and inflammation, and acts also as a modulator of gut functions. In this study, we investigated the role of adenosine A2a receptors on colonic motility in a rat model of experimental colitis.
  
  
  METHODS
  Colitis was induced by 2,4-dinitrobenzenesulfonic acid. The effects of ZM 241385 (A2a receptor antagonist) and CGS 21680 (A2a receptor agonist) were assayed on cholinergic contractions of colonic longitudinal muscle preparations evoked by transmural electrical stimulation (TES) or carbachol. A2a receptor expression in colonic neuromuscular layers was assessed by reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  ZM 241385 increased TES-induced contractions in the absence or in the presence of colitis, the drug being more effective in colonic preparations from inflamed animals. The enhancing effects of ZM 241385 were unaffected by guanethidine or alpha-chimotrypsin, whereas being prevented by Nomega-propyl-L-arginine (neuronal nitric oxide synthase inhibitor) or adenosine 5'-(alpha,beta-methylene) diphosphate (ecto-5'-nucleotidase inhibitor). Upon exposure of colonic tissues from normal or inflamed rats to dipyridamole plus adenosine deaminase, to abate endogenous adenosine levels, CGS 21680 evoked concentration-dependent reductions of contractile responses to TES, which were more intense in preparations from inflamed rats, and were antagonized by ZM 241385. Neither CGS 21680 nor ZM 241385 affected carbachol-induced contractions. Reverse transcription-polymerase chain reaction showed an increase in A2a receptor expression in colonic tissues isolated from inflamed animals.
  
  
  CONCLUSIONS
  The adenosine system is involved in neuroplastic changes occurring in inflamed gut. A2a receptors modulate the activity of colonic excitatory cholinergic nerves via facilitatory control on inhibitory nitrergic pathways, and such a regulatory function is enhanced in the presence of bowel inflammation.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Antonioli
authors.forename: Matteo
authors.initials: M
authors.lastname: Fornai
authors.forename: Rocchina
authors.initials: R
authors.lastname: Colucci
authors.forename: Narcisa
authors.initials: N
authors.lastname: Ghisu
authors.forename: Corrado
authors.initials: C
authors.lastname: Blandizzi
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D009569:Nitric Oxide; D000241:Adenosine