title: Control of enteric neuromuscular functions by purinergic A(3) receptors in normal rat distal colon and experimental bowel inflammation.
abstract: OBJECTIVE
  Adenosine A(3) receptors mediate beneficial effects in experimental colitis, but their involvement in enteric neuromuscular functions during bowel inflammation is undetermined. This study investigated the regulatory role of A(3) receptors on colonic motility in the presence of experimental colitis.
  
  
  METHODS
  Colitis was induced in rats by 2,4-dinitrobenzenesulfonic acid. A(3) receptors and adenosine deaminase (ADA, adenosine catabolic enzyme) mRNA were examined by RT-PCR. Tissue distribution of A(3) receptors was detected by confocal immunofluorescence. The effects of 2,3-ethyl-4,5-dipropyl-6-phenylpyridine-3-thiocarboxylate-5-carboxylate (MRS1523) (MRS, A(3) receptor antagonist), 2-chloro-N(6) -(3-iodobenzyl)-adenosine-5'-N-methyluronamide (2Cl-IB-MECA) (CIB, A(3) receptor agonist), dipyridamole (DIP, adenosine transport inhibitor) and ADA were assayed on contractile responses evoked by electrical stimulation (ES) or carbachol in colonic longitudinal muscle preparations (LMP).
  
  
  RESULTS
  RT-PCR showed A(3) receptors and ADA mRNA in normal colon and their increased level in inflamed tissues. Immunofluorescence showed a predominant distribution of A(3) receptors in normal myenteric ganglia and an increased density during colitis. MRS enhanced ES-induced cholinergic contractions in normal LMP, but was less effective in inflamed tissues. After pretreatment with dipyridamole plus ADA, to reduce extracellular adenosine, CIB decreased cholinergic motor responses of normal LMP to ES, with enhanced efficacy in inflamed LMP. A(3) receptor ligands did not affect carbachol-induced contractions in LMP from normal or inflamed colon.
  
  
  CONCLUSIONS
  Normally, adenosine modulated colonic cholinergic motility via activation of A(3) receptors in the myenteric plexus. A(3) receptor-mediated tonic inhibitory control by adenosine was impaired in inflamed bowel, despite increased density of functioning and pharmacologically recruitable A(3) receptors.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Internal 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: R
authors.initials: R
authors.lastname: Colucci
authors.forename: N
authors.initials: N
authors.lastname: Ghisu
authors.forename: M
authors.initials: M
authors.lastname: Tuccori
authors.forename: O
authors.initials: O
authors.lastname: Awwad
authors.forename: A
authors.initials: A
authors.lastname: Bin
authors.forename: C
authors.initials: C
authors.lastname: Zoppellaro
authors.forename: I
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: R M
authors.initials: RM
authors.lastname: Gaion
authors.forename: M C
authors.initials: MC
authors.lastname: Giron
authors.forename: C
authors.initials: C
authors.lastname: Blandizzi
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001557:Benzenesulfonates; D002217:Carbachol / Q000494:pharmacology; D003092:Colitis / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005455:Fluorescent Antibody Technique / Q000379:methods; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001557:Benzenesulfonates; D012333:RNA, Messenger; D043684:Receptor, Adenosine A3; C001073:2,4-dinitrobenzenesulfonic acid; D002217:Carbachol; D000243:Adenosine Deaminase; D000241:Adenosine