title: Endothelin-1 stimulates sphincter of Oddi motility and decreases trans-sphincteric flow: a possible mechanism contributes to cholestasis in disease states.
abstract: Endothelin-1 (ET-1) is a potent stimulator of gallbladder contractility. Its role in modulation of sphincter of Oddi (SO) motility and trans-sphincteric flow (TSF) has not been evaluated. To characterize the effects of ET-1 on SO motility and TSF, 10 anaesthetized Australian possums (in vivo, n = 6) were given graded doses of ET-1 (5-200 pmol kg-1) via closed intra-arterial injection. Blood pressure, TSF and SO motility (basal pressure, phasic amplitude, contraction frequency) were analysed. For in vitro studies, eight SO rings were subjected to 10-12-10-7 mol L-1 cumulative concentrations of ET-1 in organ bath and SO motility was measured. Data are expressed as mean +/- SEM. Statistical analysis used anova. ET-1 induced a dose-related increase in blood pressure with a maximal increase of 37.5 +/- 2.5 mmHg at 200 pmol kg-1, (P < 0.001). ET-1 also increases SO basal pressure (P < 0.001) and contraction frequency (P < 0.0001). However, the contraction amplitude was not significantly affected. ET-1 decreased TSF in a dose-related manner (P < 0.001) with cessation of TSF at the highest dose (P < 0.001). In vitro studies showed a significant increase in mean SO motility index, and frequency of contractions at higher ET-1 concentrations (10-9-10-7 mol L-1). ET-1 is a potent stimulator of SO motility resulting in a reduction in TSF.
authors.affiliation: Department of General and Digestive Surgery, Centre for Digestive Sciences, Flinders University, Flinders Medical Centre, Australia. john.chen@flinders.edu.au
authors.forename: J W C
authors.initials: JW
authors.lastname: Chen
authors.forename: A C
authors.initials: AC
authors.lastname: Schloithe
authors.forename: J
authors.initials: J
authors.lastname: Toouli
authors.forename: G T P
authors.initials: GT
authors.lastname: Saccone
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000209:etiology; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009893:Opossums / Q000502:physiology*; D009924:Organ Culture Techniques; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000502:physiology*
chemical_list: D019332:Endothelin-1