title: Bee venom phospholipase A2-induced phasic contractions in mouse rectum: independent roles of eicosanoid and gap junction proteins and their loss in experimental colitis.
abstract: Various events including digestion and inflammation are regulated by secreted phospholipase A2 (sPLA2) in gastrointestinal tissues, however, the role of sPLA2 on contractile activity has not been elucidated. We investigated the effect of bee venom PLA2 (bvPLA2), which is homologous to the central domain of group III sPLA2, on contractile activity in mouse rectum. The longitudinal preparations of rectum showed rhythmic phasic contractions (RPCs) with varied amplitude and high frequency. Treatment with bvPLA2 at 1 μg/ml increased amplitudes of RPCs without marked changes in frequency and basal tone. RPCs by bvPLA2 were affected neither by atropine nor by inhibition of nitric oxide synthase, and partly inhibited by dual inhibition of the cyclooxygenase and lipoxygenase pathways. Pretreatment of bvPLA2 with dithiothreitol, which inhibits the enzyme activity, partly reduced bvPLA2-induced RPCs, and arachidonic acid-increased RPCs were completely abolished by cyclooxygenase/lipoxygenase inhibition. Phasic contractions have been shown to be regulated by gap junction and to be decreased in gastrointestinal tissues with experimental colitis. Treatment with inhibitors of gap junction proteins, 50 μM 18β-glycyrrhetinic acid and 100 μM carbenoxolone, partly and almost completely reduced bvPLA2-induced RPCs without and with the cyclooxygenase/lipoxygenase inhibitors, respectively, but not arachidonic acid-induced RPCs. In rectum from mouse having colitis, where total levels and modified forms of connexin43 increased, bvPLA2-induced RPCs were markedly decreased. Our results suggest that both arachidonic acid metabolism and gap junction proteins independently regulated the sPLA2-induced RPCs in mouse rectum. An increased expression and/or modification of connexin43 may influence sPLA2-induced RPCs in rectum with colitis.
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: Ryouya
authors.initials: R
authors.lastname: Nomura
authors.forename: Madoka
authors.initials: M
authors.lastname: Yanagihara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sato
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: Shuonan
authors.initials: S
authors.lastname: Chen
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Fujino
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ueno
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Murayama
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000201:enzymology*; D018723:Bethanechol / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D003092:Colitis / Q000378:metabolism / Q000503:physiopathology*; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016264:Dextran Sulfate / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D054467:Phospholipases A2 / Q000494:pharmacology*; D012007:Rectum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D001514:Bee Venoms; D018031:Connexin 43; D015777:Eicosanoids; D018723:Bethanechol; C119129:18alpha-glycyrrhetinic acid; D016264:Dextran Sulfate; D054467:Phospholipases A2; D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid
keywords: Arachidonic acid; Bee venom PLA(2); Gap junction proteins; Rhythmic phasic contractions; Ulcerative colitis