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Raúl A. Marinelli - One of the best experts on this subject based on the ideXlab platform.

  • endothelin 1 and 3 induce choleresis in the rat through etb receptors coupled to nitric oxide and vagovagal reflexes
    Clinical Science, 2013
    Co-Authors: Myrian R Rodriguez, Leandro R Soria, Maria Silvia Ventimiglia, Ana Clara Najenson, Adrian Di Maria, Paula C Dabas, Andrea L Fellet, Raúl A. Marinelli
    Abstract:

    We have reported previously that centrally applied ET (endothelin)-1 and ET-3 induce either choleresis or cholestasis depending on the dose. In the present study, we sought to establish the role of these endothelins in the short-term peripheral regulation of Bile Secretion in the rat. Intravenously infused endothelins induced significant choleresis in a dose-dependent fashion, ET-1 being more potent than ET-3. Endothelins (with the exception of a higher dose of ET-1) did not affect BP (blood pressure), portal venous pressure or portal blood flow. ET-1 and ET-3 augmented the biliary excretion of Bile salts, glutathione and electrolytes, suggesting enhanced Bile acid-dependent and -independent Bile flows. ET-induced choleresis was mediated by ETB receptors coupled to NO and inhibited by truncal vagotomy, atropine administration and capsaicin perivagal application, supporting the participation of vagovagal reflexes. RT (reverse transcription)–PCR and Western blot analysis revealed ETA and ETB receptor expression in the vagus nerve. Endothelins, through ETB receptors, augmented the hepatocyte plasma membrane expression of Ntcp (Na+/taurocholate co-transporting polypeptide; Slc10a1), Bsep (Bile-salt export pump; Abcb11), Mrp2 (multidrug resistance protein-2; Abcc2) and Aqp8 (aquaporin 8). Endothelins also increased the mRNAs of these transporters. ET-1 and ET-3 induced choleresis mediated by ETB receptors coupled to NO release and vagovagal reflexes without involving haemodynamic changes. Endothelin-induced choleresis seems to be caused by increased plasma membrane translocation and transcriptional expression of key Bile transporters. These findings indicate that endothelins are able to elicit haemodynamic-independent biological effects in the liver and suggest that these peptides may play a beneficial role in pathophysiological situations where Bile Secretion is impaired. Abbreviations: AQP8, aquaporin 8; BP, blood pressure; Bsep, Bile-salt export pump; ET, endothelin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; L-NAME, NG-nitro-L-arginine methyl ester; Mrp2, multidrug resistance protein-2; Ntcp, Na+/taurocholate co-transporting polypeptide; NOS, nitric oxide synthase; qPCR, quantitative real-time PCR; PBF, portal blood flow; RT, reverse transcription; SNS, sympathetic nervous system

  • endothelin 1 and 3 induce choleresis in the rat through etb receptors coupled to nitric oxide and vagovagal reflexes
    Clinical Science, 2013
    Co-Authors: Myrian R Rodriguez, Leandro R Soria, Maria Silvia Ventimiglia, Ana Clara Najenson, Adrian Di Maria, Paula C Dabas, Andrea L Fellet, Raúl A. Marinelli
    Abstract:

    We have reported previously that centrally applied ET (endothelin)-1 and ET-3 induce either choleresis or cholestasis depending on the dose. In the present study, we sought to establish the role of these endothelins in the short-term peripheral regulation of Bile Secretion in the rat. Intravenously infused endothelins induced significant choleresis in a dose-dependent fashion, ET-1 being more potent than ET-3. Endothelins (with the exception of a higher dose of ET-1) did not affect BP (blood pressure), portal venous pressure or portal blood flow. ET-1 and ET-3 augmented the biliary excretion of Bile salts, glutathione and electrolytes, suggesting enhanced Bile acid-dependent and -independent Bile flows. ET-induced choleresis was mediated by ETB receptors coupled to NO and inhibited by truncal vagotomy, atropine administration and capsaicin perivagal application, supporting the participation of vagovagal reflexes. RT (reverse transcription)–PCR and Western blot analysis revealed ETA and ETB receptor expression in the vagus nerve. Endothelins, through ETB receptors, augmented the hepatocyte plasma membrane expression of Ntcp (Na+/taurocholate co-transporting polypeptide; Slc10a1), Bsep (Bile-salt export pump; Abcb11), Mrp2 (multidrug resistance protein-2; Abcc2) and Aqp8 (aquaporin 8). Endothelins also increased the mRNAs of these transporters. ET-1 and ET-3 induced choleresis mediated by ETB receptors coupled to NO release and vagovagal reflexes without involving haemodynamic changes. Endothelin-induced choleresis seems to be caused by increased plasma membrane translocation and transcriptional expression of key Bile transporters. These findings indicate that endothelins are able to elicit haemodynamic-independent biological effects in the liver and suggest that these peptides may play a beneficial role in pathophysiological situations where Bile Secretion is impaired. Abbreviations: AQP8, aquaporin 8; BP, blood pressure; Bsep, Bile-salt export pump; ET, endothelin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; L-NAME, NG-nitro-L-arginine methyl ester; Mrp2, multidrug resistance protein-2; Ntcp, Na+/taurocholate co-transporting polypeptide; NOS, nitric oxide synthase; qPCR, quantitative real-time PCR; PBF, portal blood flow; RT, reverse transcription; SNS, sympathetic nervous system

  • expression and localization of aquaporin water channels in rat hepatocytes evidence for a role in canalicular Bile Secretion
    Journal of Biological Chemistry, 2002
    Co-Authors: Robert C Huebert, Raúl A. Marinelli, Fabiana Garcia, Patrick L Splinter, Nicholas F. Larusso
    Abstract:

    Although Bile formation requires that large volumes of water be rapidly transported across liver epithelia, including hepatocytes, the molecular mechanisms by which water is secreted into Bile are obscure. The aquaporins are a family of 10 channel-forming, integral membrane proteins of approximately 28 kDa numbered 0-9 that allow water to rapidly traverse epithelial barriers in several organs including kidney, eye, and brain. We found transcripts of three of 10 aquaporins in hepatocytes (aquaporin 8 aquaporin 9 > aquaporin 0) by reverse transcription-polymerase chain reaction and quantitative ribonuclease protection assays; immunohistochemistry confirmed the presence of these three proteins in liver. Immunoblots of subcellular fractions of hepatocytes showed enrichment of aquaporins 0 and 8 in microsomes and canalicular plasma membranes; aquaporin 9 was enriched only in basolateral plasma membranes. Immunofluorescence of hepatocyte couplets confirmed the intracellular/canalicular localization of aquaporins 0 and 8 and the basolateral localization of aquaporin 9. Upon exposure of couplets to a choleretic stimulus (i.e. dibutyryl cAMP), aquaporin 8 redistributed to the canalicular plasma membrane; the subcellular distributions of aquaporins 0 and 9 were unaffected. In addition, exposure of couplets to dibutyryl cAMP caused an increase in canalicular water transport in the presence and absence of an osmotic gradient, an effect that was blocked by aquaporin inhibitors. These results provide evidence that aquaporins are present in hepatocytes and that aquaporins are involved in agonist-stimulated canalicular Bile Secretion.

  • the water channel aquaporin 8 is mainly intracellular in rat hepatocytes and its plasma membrane insertion is stimulated by cyclic amp
    Journal of Biological Chemistry, 2001
    Co-Authors: Fabiana Garcia, Nicholas F. Larusso, Arlinet Kierbel, Cecilia M Larocca, Sergio A Gradilone, Patrick L Splinter, Raúl A. Marinelli
    Abstract:

    We previously found that water transport across hepatocyte plasma membranes occurs mainly via a non-channel mediated pathway. Recently, it has been reported that mRNA for the water channel, aquaporin-8 (AQP8), is present in hepatocytes. To further explore this issue, we studied protein expression, subcellular localization, and regulation of AQP8 in rat hepatocytes. By subcellular fractionation and immunoblot analysis, we detected an N-glycosylated band of approximately 34 kDa corresponding to AQP8 in hepatocyte plasma and intracellular microsomal membranes. Confocal immunofluorescence microscopy for AQP8 in cultured hepatocytes showed a predominant intracellular vesicular localization. Dibutyryl cAMP (Bt(2)cAMP) stimulated the redistribution of AQP8 to plasma membranes. Bt(2)cAMP also significantly increased hepatocyte membrane water permeability, an effect that was prevented by the water channel blocker dimethyl sulfoxide. The microtubule blocker colchicine but not its inactive analog lumicolchicine inhibited the Bt(2)cAMP effect on both AQP8 redistribution to cell surface and hepatocyte membrane water permeability. Our data suggest that in rat hepatocytes AQP8 is localized largely in intracellular vesicles and can be redistributed to plasma membranes via a microtubule-depending, cAMP-stimulated mechanism. These studies also suggest that aquaporins contribute to water transport in cAMP-stimulated hepatocytes, a process that could be relevant to regulated hepatocyte Bile Secretion.

  • the water channel aquaporin 8 is mainly intracellular in rat hepatocytes and its plasma membrane insertion is stimulated by cyclic amp
    Journal of Biological Chemistry, 2001
    Co-Authors: Fabiana Garcia, Nicholas F. Larusso, Arlinet Kierbel, Cecilia M Larocca, Sergio A Gradilone, Patrick L Splinter, Raúl A. Marinelli
    Abstract:

    Abstract We previously found that water transport across hepatocyte plasma membranes occurs mainly via a non-channel mediated pathway. Recently, it has been reported that mRNA for the water channel, aquaporin-8 (AQP8), is present in hepatocytes. To further explore this issue, we studied protein expression, subcellular localization, and regulation of AQP8 in rat hepatocytes. By subcellular fractionation and immunoblot analysis, we detected anN-glycosylated band of ∼34 kDa corresponding to AQP8 in hepatocyte plasma and intracellular microsomal membranes. Confocal immunofluorescence microscopy for AQP8 in cultured hepatocytes showed a predominant intracellular vesicular localization. Dibutyryl cAMP (Bt2cAMP) stimulated the redistribution of AQP8 to plasma membranes. Bt2cAMP also significantly increased hepatocyte membrane water permeability, an effect that was prevented by the water channel blocker dimethyl sulfoxide. The microtubule blocker colchicine but not its inactive analog lumicolchicine inhibited the Bt2cAMP effect on both AQP8 redistribution to cell surface and hepatocyte membrane water permeability. Our data suggest that in rat hepatocytes AQP8 is localized largely in intracellular vesicles and can be redistributed to plasma membranes via a microtubule-depending, cAMP-stimulated mechanism. These studies also suggest that aquaporins contribute to water transport in cAMP-stimulated hepatocytes, a process that could be relevant to regulated hepatocyte Bile Secretion.

Nicholas F. Larusso - One of the best experts on this subject based on the ideXlab platform.

  • aquaporins in the hepatobiliary system
    Hepatology, 2006
    Co-Authors: Anatoliy I Masyuk, Nicholas F. Larusso
    Abstract:

    The review focuses on the potential physiological and pathophysiological roles of aquaporins (AQPs), a family of water channel proteins, in the hepatobiliary system. Among 13 aquaporins (AQP0-AQP12) cloned in mammals, seven AQPs have been identified in the liver and biliary tree. Accumulating evidence suggests that AQPs are likely involved in canalicular and ductal Bile Secretion, gluconeogenesis and microbial infection and may have other novel roles that affect liver function. (Hepatology 2006;43:S75–S81.)

  • membrane microdomains in hepatocytes potential target areas for proteins involved in canalicular Bile Secretion
    Journal of Lipid Research, 2005
    Co-Authors: Pamela S Tietz, John R Jefferson, Richard E Pagano, Nicholas F. Larusso
    Abstract:

    The formation of hepatic Bile requires that water be transported across liver epithelia. Rat hepatocytes express three aquaporins (AQPs): AQP8, AQP9, and AQP0. Recognizing that cholesterol and sphingolipids are thought to promote the assembly of proteins into specialized membrane microdomains, we hypothesized that canalicular Bile Secretion involves the trafficking of vesicles to and from localized lipid-enriched microdomains in the canalicular plasma membrane. Hepatocyte plasma membranes were sonicated in Triton and centrifuged overnight on a sucrose gradient to yield a Triton-soluble pellet and a Triton-insoluble, sphingolipid-enriched microdomain fraction at the 5%/30% sucrose interface. The detergent-insoluble portion of the hepatocyte plasma membrane was enriched in alkaline phosphatase (a microdomain-positive marker) and devoid of amino-peptidase N (a microdomain-negative marker), enriched in caveolin, both AQP8 and AQP9, but negative for clathrin. The microdomain fractions contained chloride-bicarbonate anion exchanger isoform 2 and multidrug resistance-associated protein 2. Exposure of isolated hepatocytes to glucagon increased the expression of AQP8 but not AQP9 in the microdomain fractions. Sphingolipid analysis of the insoluble fraction showed the predominant species to be sphingomyelin. These data support the presence of sphingolipid-enriched microdomains of the hepatocyte membrane that represent potential localized target areas for the clustering of AQPs and functionally related proteins involved in canalicular Bile Secretion.

  • somatostatin stimulates ductal Bile absorption and inhibits ductal Bile Secretion in mice via sstr2 on cholangiocytes
    American Journal of Physiology-cell Physiology, 2003
    Co-Authors: Ai Yu Gong, Patrick L Splinter, Pamela S Tietz, Robert C Huebert, Melissa A Muff, Mathias Z Strowski, Xian Ming Chen, Nicholas F. Larusso
    Abstract:

    With an in vitro model using enclosed intrahepatic Bile duct units (IBDUs) isolated from wild-type and somatostatin receptor (SSTR) subtype 2 knockout mice, we tested the effects of somatostatin, s...

  • expression and localization of aquaporin water channels in rat hepatocytes evidence for a role in canalicular Bile Secretion
    Journal of Biological Chemistry, 2002
    Co-Authors: Robert C Huebert, Raúl A. Marinelli, Fabiana Garcia, Patrick L Splinter, Nicholas F. Larusso
    Abstract:

    Although Bile formation requires that large volumes of water be rapidly transported across liver epithelia, including hepatocytes, the molecular mechanisms by which water is secreted into Bile are obscure. The aquaporins are a family of 10 channel-forming, integral membrane proteins of approximately 28 kDa numbered 0-9 that allow water to rapidly traverse epithelial barriers in several organs including kidney, eye, and brain. We found transcripts of three of 10 aquaporins in hepatocytes (aquaporin 8 aquaporin 9 > aquaporin 0) by reverse transcription-polymerase chain reaction and quantitative ribonuclease protection assays; immunohistochemistry confirmed the presence of these three proteins in liver. Immunoblots of subcellular fractions of hepatocytes showed enrichment of aquaporins 0 and 8 in microsomes and canalicular plasma membranes; aquaporin 9 was enriched only in basolateral plasma membranes. Immunofluorescence of hepatocyte couplets confirmed the intracellular/canalicular localization of aquaporins 0 and 8 and the basolateral localization of aquaporin 9. Upon exposure of couplets to a choleretic stimulus (i.e. dibutyryl cAMP), aquaporin 8 redistributed to the canalicular plasma membrane; the subcellular distributions of aquaporins 0 and 9 were unaffected. In addition, exposure of couplets to dibutyryl cAMP caused an increase in canalicular water transport in the presence and absence of an osmotic gradient, an effect that was blocked by aquaporin inhibitors. These results provide evidence that aquaporins are present in hepatocytes and that aquaporins are involved in agonist-stimulated canalicular Bile Secretion.

  • the water channel aquaporin 8 is mainly intracellular in rat hepatocytes and its plasma membrane insertion is stimulated by cyclic amp
    Journal of Biological Chemistry, 2001
    Co-Authors: Fabiana Garcia, Nicholas F. Larusso, Arlinet Kierbel, Cecilia M Larocca, Sergio A Gradilone, Patrick L Splinter, Raúl A. Marinelli
    Abstract:

    We previously found that water transport across hepatocyte plasma membranes occurs mainly via a non-channel mediated pathway. Recently, it has been reported that mRNA for the water channel, aquaporin-8 (AQP8), is present in hepatocytes. To further explore this issue, we studied protein expression, subcellular localization, and regulation of AQP8 in rat hepatocytes. By subcellular fractionation and immunoblot analysis, we detected an N-glycosylated band of approximately 34 kDa corresponding to AQP8 in hepatocyte plasma and intracellular microsomal membranes. Confocal immunofluorescence microscopy for AQP8 in cultured hepatocytes showed a predominant intracellular vesicular localization. Dibutyryl cAMP (Bt(2)cAMP) stimulated the redistribution of AQP8 to plasma membranes. Bt(2)cAMP also significantly increased hepatocyte membrane water permeability, an effect that was prevented by the water channel blocker dimethyl sulfoxide. The microtubule blocker colchicine but not its inactive analog lumicolchicine inhibited the Bt(2)cAMP effect on both AQP8 redistribution to cell surface and hepatocyte membrane water permeability. Our data suggest that in rat hepatocytes AQP8 is localized largely in intracellular vesicles and can be redistributed to plasma membranes via a microtubule-depending, cAMP-stimulated mechanism. These studies also suggest that aquaporins contribute to water transport in cAMP-stimulated hepatocytes, a process that could be relevant to regulated hepatocyte Bile Secretion.

Michael Trauner - One of the best experts on this subject based on the ideXlab platform.

  • role of nuclear receptors for Bile acid metabolism Bile Secretion cholestasis and gallstone disease
    Biochimica et Biophysica Acta, 2011
    Co-Authors: Thierry Claudel, Gernot Zollner, Martin Wagner, Michael Trauner
    Abstract:

    Abstract Nuclear receptors (NRs) play a key role in the transcriptional control of critical steps of hepatobiliary transport and phase I/II metabolism of endo- and xenobiotics such as Bile acids and drugs. Apart from these metabolic roles, NRs may also play a key role in the control of hepatic inflammation. Hereditary and acquired alterations of NRs contribute to our understanding of the pathogenesis of cholestasis and gallstone disease. Moreover, NRs may represent attractive drug targets for these disorders. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.

  • fxr but not tgr5 activation stimulates hco3 rich Bile Secretion and ameliorates liver damage in mdr2 abcb4 mouse model of chronic liver injury
    Hepatology, 2011
    Co-Authors: Anna Baghdasaryan, Thierry Claudel, J Gumhold, Dagmar Silbert, Luciano Adorini, Frank J Gonzalez, Kristina Schoonjans, Peter Fickert, Michael Trauner
    Abstract:

    Reference EPFL-CONF-170826View record in Web of Science Record created on 2011-12-16, modified on 2017-05-12

  • new molecular insights into the mechanisms of cholestasis
    Journal of Hepatology, 2009
    Co-Authors: Martin Wagner, Gernot Zollner, Michael Trauner
    Abstract:

    Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal Bile Secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibility and disease progression in acquired cholestatic disorders. Cholestasis is associated with complex transcriptional and post-transcriptional alterations of hepatobiliary transporters and enzymes participating in Bile formation. Ligand-activated nuclear receptors for Bile acids and other biliary compounds play a key role in the regulation of genes required for Bile formation. Pharmacological interventions in cholestasis may aim at modulating such novel regulatory pathways. This review will summarize the principles of molecular alterations in cholestasis and will give an overview of potential clinical implications.

  • mdr3 abcb4 defects a paradigm for the genetics of adult cholestatic syndromes
    Seminars in Liver Disease, 2007
    Co-Authors: Michael Trauner, Peter Fickert, Martin Wagner
    Abstract:

    Because ATP-binding cassette (ABC) transporters are important for normal Bile Secretion, hereditary and acquired ABC transporter defects play a central role in the pathogenesis of cholestasis. Defects of the phospholipid export pump MDR3 ( ABCC4) result in impaired biliary excretion of phosphatidylcholine and a variety of cholestatic syndromes ranging from progressive familial intrahepatic cholestasis in neonates to biliary cirrhosis in adults. Moreover, MDR3 mutations predispose to cholestasis of pregnancy and drug-induced cholestasis. Because MDR2 (rodent orthologue of human MDR3) knockout mice develop sclerosing cholangitis, it is attractive to speculate that MDR3 defects could also play an important role in cholangiopathies in humans. Indeed, MDR3 variants could play a role as modifier gene in primary biliary cirrhosis and primary sclerosing cholangitis, but their exact role needs further clarification. Impaired biliary phosphatidylcholine excretion has also been reported in total parenteral nutrition-induced cholestasis and Bile duct injury following liver transplantation, but a genetic basis for these findings remains to be explored. Several drugs for the treatment of cholestatic liver diseases target MDR3 expression and function, further underscoring the clinical significance of this transport system.

Ana Clara Najenson - One of the best experts on this subject based on the ideXlab platform.

  • endothelin 1 and 3 induce choleresis in the rat through etb receptors coupled to nitric oxide and vagovagal reflexes
    Clinical Science, 2013
    Co-Authors: Myrian R Rodriguez, Leandro R Soria, Maria Silvia Ventimiglia, Ana Clara Najenson, Adrian Di Maria, Paula C Dabas, Andrea L Fellet, Raúl A. Marinelli
    Abstract:

    We have reported previously that centrally applied ET (endothelin)-1 and ET-3 induce either choleresis or cholestasis depending on the dose. In the present study, we sought to establish the role of these endothelins in the short-term peripheral regulation of Bile Secretion in the rat. Intravenously infused endothelins induced significant choleresis in a dose-dependent fashion, ET-1 being more potent than ET-3. Endothelins (with the exception of a higher dose of ET-1) did not affect BP (blood pressure), portal venous pressure or portal blood flow. ET-1 and ET-3 augmented the biliary excretion of Bile salts, glutathione and electrolytes, suggesting enhanced Bile acid-dependent and -independent Bile flows. ET-induced choleresis was mediated by ETB receptors coupled to NO and inhibited by truncal vagotomy, atropine administration and capsaicin perivagal application, supporting the participation of vagovagal reflexes. RT (reverse transcription)–PCR and Western blot analysis revealed ETA and ETB receptor expression in the vagus nerve. Endothelins, through ETB receptors, augmented the hepatocyte plasma membrane expression of Ntcp (Na+/taurocholate co-transporting polypeptide; Slc10a1), Bsep (Bile-salt export pump; Abcb11), Mrp2 (multidrug resistance protein-2; Abcc2) and Aqp8 (aquaporin 8). Endothelins also increased the mRNAs of these transporters. ET-1 and ET-3 induced choleresis mediated by ETB receptors coupled to NO release and vagovagal reflexes without involving haemodynamic changes. Endothelin-induced choleresis seems to be caused by increased plasma membrane translocation and transcriptional expression of key Bile transporters. These findings indicate that endothelins are able to elicit haemodynamic-independent biological effects in the liver and suggest that these peptides may play a beneficial role in pathophysiological situations where Bile Secretion is impaired. Abbreviations: AQP8, aquaporin 8; BP, blood pressure; Bsep, Bile-salt export pump; ET, endothelin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; L-NAME, NG-nitro-L-arginine methyl ester; Mrp2, multidrug resistance protein-2; Ntcp, Na+/taurocholate co-transporting polypeptide; NOS, nitric oxide synthase; qPCR, quantitative real-time PCR; PBF, portal blood flow; RT, reverse transcription; SNS, sympathetic nervous system

  • endothelin 1 and 3 induce choleresis in the rat through etb receptors coupled to nitric oxide and vagovagal reflexes
    Clinical Science, 2013
    Co-Authors: Myrian R Rodriguez, Leandro R Soria, Maria Silvia Ventimiglia, Ana Clara Najenson, Adrian Di Maria, Paula C Dabas, Andrea L Fellet, Raúl A. Marinelli
    Abstract:

    We have reported previously that centrally applied ET (endothelin)-1 and ET-3 induce either choleresis or cholestasis depending on the dose. In the present study, we sought to establish the role of these endothelins in the short-term peripheral regulation of Bile Secretion in the rat. Intravenously infused endothelins induced significant choleresis in a dose-dependent fashion, ET-1 being more potent than ET-3. Endothelins (with the exception of a higher dose of ET-1) did not affect BP (blood pressure), portal venous pressure or portal blood flow. ET-1 and ET-3 augmented the biliary excretion of Bile salts, glutathione and electrolytes, suggesting enhanced Bile acid-dependent and -independent Bile flows. ET-induced choleresis was mediated by ETB receptors coupled to NO and inhibited by truncal vagotomy, atropine administration and capsaicin perivagal application, supporting the participation of vagovagal reflexes. RT (reverse transcription)–PCR and Western blot analysis revealed ETA and ETB receptor expression in the vagus nerve. Endothelins, through ETB receptors, augmented the hepatocyte plasma membrane expression of Ntcp (Na+/taurocholate co-transporting polypeptide; Slc10a1), Bsep (Bile-salt export pump; Abcb11), Mrp2 (multidrug resistance protein-2; Abcc2) and Aqp8 (aquaporin 8). Endothelins also increased the mRNAs of these transporters. ET-1 and ET-3 induced choleresis mediated by ETB receptors coupled to NO release and vagovagal reflexes without involving haemodynamic changes. Endothelin-induced choleresis seems to be caused by increased plasma membrane translocation and transcriptional expression of key Bile transporters. These findings indicate that endothelins are able to elicit haemodynamic-independent biological effects in the liver and suggest that these peptides may play a beneficial role in pathophysiological situations where Bile Secretion is impaired. Abbreviations: AQP8, aquaporin 8; BP, blood pressure; Bsep, Bile-salt export pump; ET, endothelin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; L-NAME, NG-nitro-L-arginine methyl ester; Mrp2, multidrug resistance protein-2; Ntcp, Na+/taurocholate co-transporting polypeptide; NOS, nitric oxide synthase; qPCR, quantitative real-time PCR; PBF, portal blood flow; RT, reverse transcription; SNS, sympathetic nervous system

Maria Silvia Ventimiglia - One of the best experts on this subject based on the ideXlab platform.

  • endothelin 1 and 3 induce choleresis in the rat through etb receptors coupled to nitric oxide and vagovagal reflexes
    Clinical Science, 2013
    Co-Authors: Myrian R Rodriguez, Leandro R Soria, Maria Silvia Ventimiglia, Ana Clara Najenson, Adrian Di Maria, Paula C Dabas, Andrea L Fellet, Raúl A. Marinelli
    Abstract:

    We have reported previously that centrally applied ET (endothelin)-1 and ET-3 induce either choleresis or cholestasis depending on the dose. In the present study, we sought to establish the role of these endothelins in the short-term peripheral regulation of Bile Secretion in the rat. Intravenously infused endothelins induced significant choleresis in a dose-dependent fashion, ET-1 being more potent than ET-3. Endothelins (with the exception of a higher dose of ET-1) did not affect BP (blood pressure), portal venous pressure or portal blood flow. ET-1 and ET-3 augmented the biliary excretion of Bile salts, glutathione and electrolytes, suggesting enhanced Bile acid-dependent and -independent Bile flows. ET-induced choleresis was mediated by ETB receptors coupled to NO and inhibited by truncal vagotomy, atropine administration and capsaicin perivagal application, supporting the participation of vagovagal reflexes. RT (reverse transcription)–PCR and Western blot analysis revealed ETA and ETB receptor expression in the vagus nerve. Endothelins, through ETB receptors, augmented the hepatocyte plasma membrane expression of Ntcp (Na+/taurocholate co-transporting polypeptide; Slc10a1), Bsep (Bile-salt export pump; Abcb11), Mrp2 (multidrug resistance protein-2; Abcc2) and Aqp8 (aquaporin 8). Endothelins also increased the mRNAs of these transporters. ET-1 and ET-3 induced choleresis mediated by ETB receptors coupled to NO release and vagovagal reflexes without involving haemodynamic changes. Endothelin-induced choleresis seems to be caused by increased plasma membrane translocation and transcriptional expression of key Bile transporters. These findings indicate that endothelins are able to elicit haemodynamic-independent biological effects in the liver and suggest that these peptides may play a beneficial role in pathophysiological situations where Bile Secretion is impaired. Abbreviations: AQP8, aquaporin 8; BP, blood pressure; Bsep, Bile-salt export pump; ET, endothelin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; L-NAME, NG-nitro-L-arginine methyl ester; Mrp2, multidrug resistance protein-2; Ntcp, Na+/taurocholate co-transporting polypeptide; NOS, nitric oxide synthase; qPCR, quantitative real-time PCR; PBF, portal blood flow; RT, reverse transcription; SNS, sympathetic nervous system

  • endothelin 1 and 3 induce choleresis in the rat through etb receptors coupled to nitric oxide and vagovagal reflexes
    Clinical Science, 2013
    Co-Authors: Myrian R Rodriguez, Leandro R Soria, Maria Silvia Ventimiglia, Ana Clara Najenson, Adrian Di Maria, Paula C Dabas, Andrea L Fellet, Raúl A. Marinelli
    Abstract:

    We have reported previously that centrally applied ET (endothelin)-1 and ET-3 induce either choleresis or cholestasis depending on the dose. In the present study, we sought to establish the role of these endothelins in the short-term peripheral regulation of Bile Secretion in the rat. Intravenously infused endothelins induced significant choleresis in a dose-dependent fashion, ET-1 being more potent than ET-3. Endothelins (with the exception of a higher dose of ET-1) did not affect BP (blood pressure), portal venous pressure or portal blood flow. ET-1 and ET-3 augmented the biliary excretion of Bile salts, glutathione and electrolytes, suggesting enhanced Bile acid-dependent and -independent Bile flows. ET-induced choleresis was mediated by ETB receptors coupled to NO and inhibited by truncal vagotomy, atropine administration and capsaicin perivagal application, supporting the participation of vagovagal reflexes. RT (reverse transcription)–PCR and Western blot analysis revealed ETA and ETB receptor expression in the vagus nerve. Endothelins, through ETB receptors, augmented the hepatocyte plasma membrane expression of Ntcp (Na+/taurocholate co-transporting polypeptide; Slc10a1), Bsep (Bile-salt export pump; Abcb11), Mrp2 (multidrug resistance protein-2; Abcc2) and Aqp8 (aquaporin 8). Endothelins also increased the mRNAs of these transporters. ET-1 and ET-3 induced choleresis mediated by ETB receptors coupled to NO release and vagovagal reflexes without involving haemodynamic changes. Endothelin-induced choleresis seems to be caused by increased plasma membrane translocation and transcriptional expression of key Bile transporters. These findings indicate that endothelins are able to elicit haemodynamic-independent biological effects in the liver and suggest that these peptides may play a beneficial role in pathophysiological situations where Bile Secretion is impaired. Abbreviations: AQP8, aquaporin 8; BP, blood pressure; Bsep, Bile-salt export pump; ET, endothelin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; L-NAME, NG-nitro-L-arginine methyl ester; Mrp2, multidrug resistance protein-2; Ntcp, Na+/taurocholate co-transporting polypeptide; NOS, nitric oxide synthase; qPCR, quantitative real-time PCR; PBF, portal blood flow; RT, reverse transcription; SNS, sympathetic nervous system