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Endothelin‐1 stimulates sphincter of Oddi motility and decreases trans‐sphincteric flow: a possible mechanism contributes to cholestasis in disease states
Author(s) -
Chen J. W. C.,
Schloithe A. C.,
Toouli J.,
Saccone G. T. P.
Publication year - 2003
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1046/j.1365-2982.2003.00424.x
Subject(s) - motility , sphincter of oddi , contraction (grammar) , contractility , endocrinology , medicine , endothelin receptor , endothelin 1 , stimulation , chemistry , muscle contraction , biology , receptor , genetics
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.