title: Inosine attenuates spontaneous activity in the rat neurogenic bladder through an A2Bpathway.
abstract: Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions. In isolated tissue assays, inosine (1 mM) significantly decreased the amplitude of spontaneous activity (SA) in SCI bladder muscle strips. This effect was prevented by a pan-adenosine receptor antagonist CGS15943, but not by A1or A3receptor antagonists. The A2Aantagonist ZM241385 and A2Bantagonist PSB603 prevented the effect of inosine. The effect of inosine was mimicked by the adenosine receptor agonist NECA and the A2Breceptor agonist BAY60-6583. The inhibition of SA by inosine was not observed in the presence of the BK antagonist, iberiotoxin, but persisted in the presence of KATPand SK antagonists. These findings demonstrate that inosine acts via an A2Breceptor-mediated pathway that impinges on specific potassium channel effectors.
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Doyle
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA.|Division of Urology, VA Boston Healthcare System, West Roxbury, MA, USA.|Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Cristofaro
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Sack
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Lukianov
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Mattias
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Yeun Goo
authors.initials: YG
authors.lastname: Chung
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA.|Division of Urology, VA Boston Healthcare System, West Roxbury, MA, USA.|Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Maryrose P
authors.initials: MP
authors.lastname: Sullivan
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Rosalyn M
authors.initials: RM
authors.lastname: Adam
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000008:administration & dosage; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007288:Inosine / Q000008:administration & dosage*; D015221:Potassium Channels / Q000235:genetics; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D013449:Sulfonamides / Q000008:administration & dosage; D014227:Triazines / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D014970:Xanthines / Q000008:administration & dosage
chemical_list: D058917:Adenosine A2 Receptor Antagonists; C000592275:PSB603; D015221:Potassium Channels; D043705:Receptor, Adenosine A2A; D013449:Sulfonamides; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; D007288:Inosine