title: Dysfunction of neurogenic VIP-mediated relaxation in mouse distal colon with dextran sulfate sodium-induced colitis.
abstract: Vasoactive intestinal peptide (VIP) regulates various functions including motility and immune homeostasis in colon. The VIP system including its receptors has been established to control the development of ulcerative colitis, but the functional changes of the system-regulated motility in colon with ulcerative colitis are not well understood. In this study, we investigated VIP-related contractile responses in distal colon from mice with dextran sulfate sodium (DSS)-induced acute colitis. Electrical stimulation (ES) under our conditions caused relaxation during ES and contraction after withdrawal of ES in a tetrodotoxin-sensitive manner. Pharmacological analyses showed two phases of ES-induced relaxation: a transient neuronal nitric oxide (NO) synthase-dependent phase (I), and a continued VIP receptor-mediated phase (II). Inhibition of VIP receptors and protein kinase A decreased both phases. In colon from DSS-treated mice, ES-induced phase II (also phase I) and VIP-induced, but not cyclic AMP analog-induced, relaxation were decreased. Stimulation with VIP significantly increased cyclic AMP formation in colon preparations from control but not DSS-treated mice. In colon from DSS-treated mice, the basal cyclic AMP level was markedly greater without changes in the level of VIP receptor VPAC(2). Isoprenaline- and forskolin-induced relaxation and cyclic AMP formation were not changed by DSS treatment. These findings suggest that dysfunction of VIP receptors in muscles, in addition to loss of the neuronal VIP and NO pathways, are involved in abnormal motility in mouse colon with DSS-induced colitis.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Kato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamane
authors.forename: Ryoya
authors.initials: R
authors.lastname: Nomura
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Kimihito
authors.initials: K
authors.lastname: Tashima
authors.forename: Shunji
authors.initials: S
authors.lastname: Horie
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Fujino
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Murayama
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016264:Dextran Sulfate; D004558:Electric Stimulation; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D016264:Dextran Sulfate; D000242:Cyclic AMP; D052248:Nitric Oxide Synthase Type I; D017868:Cyclic AMP-Dependent Protein Kinases