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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Hepatología experimental > DA - CIMA - Terapia génica y Hepatología - Hepatología experimental - Artículos de revista >

Taurocholate-stimulated leukotriene C4 biosynthesis and leukotriene C4-stimulated choleresis in isolated rat liver
Authors: Rodriguez-Ortigosa, C.M. (Carlos M.)
Vesperinas, I. (Idoia)
Qian, C. (Cheng)
Quiroga, J. (Jorge)
Medina, J.F. (Juan Francisco)
Prieto, J. (Jesús)
Keywords: Cholagogues and Choleretics/pharmacology
Leukotriene C4/biosynthesis
Liver/drug effects
Taurocholic Acid/pharmacology
Issue Date: 1995
Publisher: WB Saunders
Publisher version: http://www.sciencedirect.com/science/article/pii/0016508595901426
ISSN: 1528-0012
Citation: Rodriguez-Ortigosa CM, Vesperinas I, Qian C, Quiroga J, Medina JF, Prieto J. Taurocholate-stimulated leukotriene C4 biosynthesis and leukotriene C4-stimulated choleresis in isolated rat liver. Gastroenterology 1995 Jun;108(6):1793-1801.
Abstract
BACKGROUND/AIMS: Cysteinyl-containing leukotrienes seem to exert a cholestatic effect. However, leukotriene inhibitors were found to reduce bile salt efflux in isolated rat hepatocytes, suggesting a role for leukotrienes in bile flow formation. METHODS: In the isolated rat liver, the effects of two different concentrations of leukotriene C4 on bile flow and bile salt excretion are analyzed, as well as the possible effect of taurocholate on the hepatic production of cysteinyl-containing leukotrienes. RESULTS: Leukotriene C4 (0.25 fmol) increased bile salt excretion (+22.2%; P < 0.05), whereas a much higher dose (0.25 x 10(6) fmol) showed the known cholestatic effect, reducing bile salt excretion (-25.9%; P < 0.01). These dose-dependent biphasic effects were specific because they could be prevented by the simultaneous administration of cysteinyl-containing leukotriene antagonists. On the other hand, taurocholate administration induced a dose-dependent increase in biliary excretion of cysteinyl-containing leukotrienes. Furthermore, taurocholate increased messenger RNA levels of 5-lipoxygenase, a key enzyme in leukotriene biosynthesis. Taurocholate increase of hepatocyte intracellular calcium was not significant, suggesting that taurocholate effects are not mediated by stimulation of calcium metabolism. CONCLUSIONS: These results constitute evidence for the existence of a positive feedback mechanism by which bile salts stimulate the synthesis of leukotrienes that, in turn, stimulate bile salt excretion.
Permanent link: http://hdl.handle.net/10171/23288
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Hepatología experimental - Artículos de revista

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