title: Involvement of the P2X7 purinergic receptor in colonic motor dysfunction associated with bowel inflammation in rats.
abstract: OBJECTIVE
  Recent evidence indicates an involvement of P2X7 purinergic receptor (P2X7R) in the fine tuning of immune functions, as well as in driving enteric neuron apoptosis under intestinal inflammation. However, the participation of this receptor in the regulation of enteric neuromuscular functions remains undetermined. This study was aimed at investigating the role of P2X7Rs in the control of colonic motility in experimental colitis.
  
  
  METHODS
  Colitis was induced in rats by 2,4-dinitrobenzenesulfonic acid. P2X7R distribution was examined by immunofluorescence analysis. The effects of A804598 (selective P2X7R antagonist) and BzATP (P2X7R agonist) were tested on contractions of longitudinal smooth muscle evoked by electrical stimulation or by carbachol in the presence of tetrodotoxin.
  
  
  RESULTS
  P2X7Rs were predominantly located in myenteric neurons, but, in the presence of colitis, their expression increased in the neuromuscular layer. In normal preparations, A804598 elicited a negligible increase in electrically induced contractions, while a significant enhancement was recorded in inflamed tissues. In the presence of Nω-propyl-L-arginine (NPA, neuronal nitric oxide synthase inhibitor) the A804598 effects were lost. P2X7R stimulation with BzATP did not significantly affect electrical-induced contractions in normal colon, while a marked reduction was recorded under inflammation. The inhibitory effect of BzATP was antagonized by A804598, and it was also markedly blunted by NPA. Both P2X7R ligands did not affect carbachol-induced contractions.
  
  
  CONCLUSIONS
  The purinergic system contributes to functional neuromuscular changes associated with bowel inflammation via P2X7Rs, which modulate the activity of excitatory cholinergic nerves through a facilitatory control on inhibitory nitrergic pathways.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Antonioli
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Giron
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Rocchina
authors.initials: R
authors.lastname: Colucci
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Pellegrini
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Sacco
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Caputi
authors.affiliation: Scientific Institute IRCCS Eugenio Medea, Conegliano, Treviso, Italy.
authors.forename: Genny
authors.initials: G
authors.lastname: Orso
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tuccori
authors.affiliation: Laboratory of Clinical Pharmacology, University of Parma, Parma, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Scarpignato
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Blandizzi
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fornai
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001557:Benzenesulfonates / Q000009:adverse effects; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: C539459:2-cyano-1-((1S)-1-phenylethyl)-3-quinolin-5-ylguanidine; D001557:Benzenesulfonates; D006146:Guanidines; D058911:Purinergic P2X Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D011804:Quinolines; D058486:Receptors, Purinergic P2X7; C001073:2,4-dinitrobenzenesulfonic acid; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate