title: Aminophylline suppresses stress-induced visceral hypersensitivity and defecation in irritable bowel syndrome.
abstract: Pharmacological therapy for irritable bowel syndrome (IBS) has not been established. In order to find candidate drugs for IBS with diarrhea (IBS-D), we screened a compound library of drugs clinically used for their ability to prevent stress-induced defecation and visceral hypersensitivity in rats. We selected the bronchodilator aminophylline from this library. Using a specific inhibitor for each subtype of adenosine receptors (ARs) and phosphodiesterases (PDEs), we found that both A2BARs and PDE4 are probably mediated the inhibitory effect of aminophylline on wrap restraint stress (WRS)-induced defecation. Aminophylline suppressed maternal separation- and acetic acid administration-induced visceral hypersensitivity to colorectal distension (CRD), which was mediated by both A2AARs and A2BARs. We propose that aminophylline is a candidate drug for IBS-D because of its efficacy in both of stress-induced defecation and visceral hypersensitivity, as we observed here, and because it is clinically safe.
authors.affiliation: Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8512, Japan.
authors.forename: Teita
authors.initials: T
authors.lastname: Asano
authors.affiliation: Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-2αhinmachi, Nishitokyo-shi, 202-8585, Japan.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Tanaka
authors.affiliation: Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Tada
authors.affiliation: Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Shimamura
authors.affiliation: Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Rikako
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Maruoka
authors.affiliation: Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8512, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Takenaga
authors.affiliation: LTT Bio-Pharma Co., Ltd, Shiodome Building 3F, 1-2-20 Kaigan, Minato-ku, Tokyo 105-0022, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000628:Aminophylline / Q000008:administration & dosage*; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D003967:Diarrhea / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D005765:Gastrointestinal Agents; D000628:Aminophylline