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| 1 | Hepatic drug transporters and nuclear receptors:Regulation by therapeutic agents显示文摘The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators. | Aldo D Mottino Viviana A Catania | 2008 | World Journal of Gastroenterology2008，14，46： | 5 |
| 2 | Dynamic localization of hepatocellular transporters in health and disease显示文摘Vesicle-based traffi cking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal,submembrane compartment,followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane,the transporters usually undergo recycling between the plasma membrane and the endosomal compartment,which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence,it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters,which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis,and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation,with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition,the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally,several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP,tauroursodeoxycholate) are described. | Marcelo G Roma Fernando A Crocenzi Aldo D Mottino | 2008 | World Journal of Gastroenterology2008，14，44： | 2 |
| 3 | In vivo anti-complement effect of bilirubin-IXalpha显示文摘 | Arriaga S Almara A Mottino A | 2002 | Biochem Pharmacol2002，64，4： | 1 |
| 4 | In vivo anti-complement effect of bilirubinixalpha显示文摘 | Arriaga S Almara A Mottino A | 2002 | Biochem Pharmacol2002，64，： | 1 |
| 5 | In vivo anti-complement effect of bilirubinixalpha显示文摘 | Arriaga S Almara A Mottino A | 2002 | Biochem Pharmacol2002，64，： | 1 |
| 6 | Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat显示文摘 | Crocenzi FA Mottino AD Sanchez Pozzi EJ | 2003 | Gut2003，52，8： | 1 |
| 7 | In vivo anti- complement effect of bilir ubinixalpha显示文摘 | Arriaga S Almara A Mottino A | 2002 | Biochem Pharmacol2002，64，： | 1 |
| 8 | In vivo anti-complement effect of bilirubin-IX alpha 显示文摘 | Arriaga S Almara A Mottino A | 2002 | Biochem Pharmacol2002，64，4： | 1 |
| 9 | In vivo anti-com- plement effect of bilirubin-IXalpha显示文摘 | ARRIAGA S ALMARA A MOTTINO A | 2002 | Biochem Pharmacol2002，64，4： | 1 |
| 10 | In vivo anti-complement effect of bilirubin-Ⅸalpha显示文摘 | Arriaga S Almara A Mottino A | 2002 | Biochem Pharmacol2002，64，： | 1 |
| 11 | Expression and localiza- tion of multidrng resistant protein mrp2 in rat small intestine 显示文摘 | Mottino A D Hoffman T Jennes L | 2000 | Journal of Pharmacology and Experimental Therapeutics2000，293，3： | 1 |
| 12 | Differential effects of silymarin and its active component silibininon plasma membrane stability and hepatocellularlysis显示文摘 | BASIGLIO CL SANCHEZ POZZI EJ MOTTINO AD | 2009 | ChemBiol Interact2009，179，23： | 1 |
| 13 | Differential effects of silymarin and its active component silibinin on plasma mem- brane stability and hepatocellular lysis显示文摘 | Basiglio CL Sanchez Pozzi EJ Mottino AD | 2009 | Chemico-biological inter- actions2009，179，2： | 1 |
| 14 | Expression and localization of multidrug resistant protein mrp2 in rat small intestine显示文摘 | Mottino AD Hoffman T Jennes L | 2000 | J Pharmacol Exp Ther2000，293，3： | 1 |
| 15 | Differential effects of silymarin and its active component silibinin on plasma membrance stability and hepatocellular lysis显示文摘 | Basiglio CL Sánchez Pozzi EJ Mottino AD Roma MG | 2009 | Chem Biol Interact2009，179，23： | 1 |
| 16 | Expression and localization of multidrug resistant protein mrp2 in rat small intestine显示文摘 | Mottino AD Hoffman T Jennes L | | 0，，3： | 1 |
| 17 | In vivo anti- complement effect of bilirubin - IXalpha 显示文摘 | Arriaga S Almara A Mottino A | 2002 | Biochem Pharmacol2002，64，4： | 1 |
| 18 | Dif- ferential effects of silymarin and its active component silibinin on plasma membrane stability and hepatocellular lysis显示文摘 | Basiglio CL S~tnchez Pozzi EJ Mottino AD | 2009 | Chem Biol Interact2009，179，23： | 1 |
| 19 | In vivo anti-complement effect of bilirubinixalpha 显示文摘 | Arriaga S Almara A Mottino A | 2002 | Biochem Pharmacol2002，64，4： | 1 |
| 20 | Expression and localization of multidrug resistant protein mrp2 in rat small intestine显示文摘 | Mottino AD Hoffman T Jennes L | 2000 | J Pharmacol Exp Ther2000，293，3： | 1 |
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