title: Decrease of guanylyl cyclase β1 subunit and nitric oxide (NO)-induced relaxation in mouse rectum with colitis and its reproduction on long-term NO treatment.
abstract: Nitric oxide (NO) influences motility in the colon in patients with ulcerative colitis, but the exact mechanism involved remains unknown. Colitis was induced in mice by the oral administration of 2.5% dextran sodium sulfate (DSS), and the motility in longitudinal preparations from rectum and distal colon and expression of β1 subunit of soluble guanylyl cyclase (sGCβ1) were analyzed. Electrical stimulation (ES) caused a transient relaxation via the NO pathway in both rectum and colon from control mice. Stimulation with sodium nitroprusside (SNP) caused relaxation in the two regions, and the half-time (T                         (1/2)) of the maximal relaxation induced by 100 μM SNP was 8.1 ± 1.0 s in rectum. DSS treatment (1) abolished the ES-induced relaxation, but not dibutyryl cyclic GMP-induced response, in both regions, (2) decreased the maximal response to SNP accompanied by a loss of immunoreactive sGCβ1 protein in rectum, but did not affect the amplitude of the relaxant response or the protein in distal colon, and (3) caused an increase in the T                         (1/2) value in response to SNP in both regions. Pretreatment of both preparations from control mice with 600 μM SNP for 30 min decreased both ES- and SNP-induced relaxation, SNP-induced cyclic GMP formation, and immunoreactive sGCβ1 levels. NO-mediated relaxation was impaired by a dysfunctional sGC with and without a loss of immunoreactivity to sGCβ1 in rectum and colon from DSS-treated mice, respectively. Long-term exposure of the tissues with an excess amount of NO changes the sGC-mediated relaxation.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Hamada
authors.forename: Erina
authors.initials: E
authors.lastname: Kato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Fujino
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: Toshihiko
authors.initials: T
authors.lastname: Murayama
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006152:Cyclic GMP / Q000378:metabolism; D016264:Dextran Sulfate; D004558:Electric Stimulation; D006162:Guanylate Cyclase / Q000502:physiology*; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D012007:Rectum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D000071756:Soluble Guanylyl Cyclase
chemical_list: D020030:Nitric Oxide Donors; D018160:Receptors, Cytoplasmic and Nuclear; D009599:Nitroprusside; D009569:Nitric Oxide; D016264:Dextran Sulfate; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP