Abstract

Two major processes presumably located in the bile canalicular membrane initate and regulate hepatic bile flow. The present study is designed to examine the role of the putative bile acid receptor and the sodium pump, (Na-K)ATPase, in the regulation of bile flow. The importance of sodium gradients in the regulation of bile acid membrane translocation will be examined in hepatocytes, ileal and renal tubule cells. Bile acid receptors and (Na-K)ATPase will be quantitated under different pharmacological situations which are associated with altered bile flow. Transport of bile acids into cultured hepatocytes will be studied under defined conditions. Membrane vesicles will be prepared from hepatocytes, ileum and renal tubular cells to examine membrane transport in contra-lateral poles of the cell. The effect of phenobarbital, glucocorticoids, estrogens and thyroid hormone and high cholesterol diets on liver surface membrane structure and function will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK015851-15
Application #
3225456
Study Section
(SSS)
Project Start
1978-08-01
Project End
1990-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
15
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Qadri, Ishtiaq; Hu, Ling-Jia; Iwahashi, Mieko et al. (2009) Interaction of hepatocyte nuclear factors in transcriptional regulation of tissue specific hormonal expression of human multidrug resistance-associated protein 2 (abcc2). Toxicol Appl Pharmacol 234:281-92
Qadri, Ishtiaq; Iwahashi, Mieko; Kullak-Ublick, Gerd A et al. (2006) Hepatocyte nuclear factor (HNF) 1 and HNF4 mediate hepatic multidrug resistance protein 2 up-regulation during hepatitis C virus gene expression. Mol Pharmacol 70:627-36
Simon, Francis R; Iwahashi, Mieko; Hu, Ling-Jia et al. (2006) Hormonal regulation of hepatic multidrug resistance-associated protein 2 (Abcc2) primarily involves the pattern of growth hormone secretion. Am J Physiol Gastrointest Liver Physiol 290:G595-608
Qadri, Ishtiaq; Iwahashi, Mieko; Capasso, Juan M et al. (2004) Induced oxidative stress and activated expression of manganese superoxide dismutase during hepatitis C virus replication: role of JNK, p38 MAPK and AP-1. Biochem J 378:919-28
Simon, Francis R; Fortune, John; Iwahashi, Mieko et al. (2004) Multihormonal regulation of hepatic sinusoidal Ntcp gene expression. Am J Physiol Gastrointest Liver Physiol 287:G782-94
Reichard, John F; Doorn, Jonathan A; Simon, Franz et al. (2003) Characterization of multidrug resistance-associated protein 2 in the hepatocellular disposition of 4-hydroxynonenal. Arch Biochem Biophys 411:243-50
Qadri, Ishtiaq; Iwahashi, Mieko; Simon, Francis (2002) Hepatitis C virus NS5A protein binds TBP and p53, inhibiting their DNA binding and p53 interactions with TBP and ERCC3. Biochim Biophys Acta 1592:193-204
Simon, Francis R; Fortune, John; Iwahashi, Mieko et al. (2002) Sexual dimorphic expression of ADH in rat liver: importance of the hypothalamic-pituitary-liver axis. Am J Physiol Gastrointest Liver Physiol 283:G646-55
Fiedler, J; Simon, F R; Iwahashi, M et al. (2001) Effect of peroxisome proliferator-activated receptor alpha activation on leukotriene B4 metabolism in isolated rat hepatocytes. J Pharmacol Exp Ther 299:691-7
Shiao, T; Iwahashi, M; Fortune, J et al. (2000) Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter. Genomics 69:203-13

Showing the most recent 10 out of 19 publications