title: Adenosine-mediated enteric neuromuscular function is affected during herpes simplex virus type 1 infection of rat enteric nervous system.
abstract: Adenosine plays an important role in regulating intestinal motility and inflammatory processes. Previous studies in rodent models have demonstrated that adenosine metabolism and signalling are altered during chronic intestinal inflammatory diseases. However, the involvement of the adenosinergic system in the pathophysiology of gut dysmotility associated to a primary neurodysfunction is still unclear. Recently, we showed that the neurotropic Herpes simplex virus type-1 (HSV-1), orally inoculated to rodents, infects the rat enteric nervous system (ENS) and affects gut motor function without signs of systemic infection. In this study we examined whether changes in purinergic metabolism and signaling occur during permanent HSV-1 infection of rat ENS. Using isolated organ bath assays, we found that contraction mediated by adenosine engagement of A1 or A2A receptors was impaired at 1 and 6 weeks post-viral administration. Immunofluorescence studies revealed that viral infection of ENS led to a marked redistribution of adenosine receptors: A1 and A2B receptors were confined to the muscle layers whereas A2A and A3 receptors were expressed mainly in the myenteric plexus. Viral-induced ENS neurodysfunction influenced adenosine metabolism by increasing adenosine deaminase and CD73 levels in longitudinal muscle-myenteric plexus with no sign of frank inflammation. This study provides the first evidence for involvement of the adenosinergic system during HSV-1 infection of the ENS. As such, this may represent a valid therapeutic target for modulating gut contractility associated to a primary neurodysfunction.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zoppellaro
authors.forename: Anna
authors.initials: A
authors.lastname: Bin
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.forename: Serena
authors.initials: S
authors.lastname: Banzato
authors.forename: Veronica
authors.initials: V
authors.lastname: Macchi
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Giron
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D002522:Chlorocebus aethiops; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006561:Herpes Simplex / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018259:Herpesvirus 1, Human; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009197:Myenteric Plexus / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D008565:Membrane Proteins; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; C548484:Ada protein, rat; D000243:Adenosine Deaminase; D000241:Adenosine