Live animals, perfused organs, isolated cells, and artificial membranes are used to explore the physiology of bile formation and hepatic solute transport at a fundamental level. There is a strong emphasis on biophysical techniques, mathematical modeling, and computer simulation to achieve these objectives. The long term goal is to understand the pathogenesis of such human afflictions as cholestasis and cholelithiasis, the effect of these diseases on the normal excretion and metabilism of endogenous products like bilirubin, bile acids, and long chain fatty acids and to elucidate the pharmacokinetics of hepatic drug disposal. More immediate objectives are to devise and validate new ways to measure the rate constants for hepatic transport and to unravel the mystery of how the liver deals efficiently with organic solutes that arrive in the afferent circulation bound to plasma proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK027623-11
Application #
3483504
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1980-01-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
11
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Cai, Z S; Luxon, B A; Forker, E L (1995) Intralobular zonal heterogeneity and hepatic indicator dilution curves. Am J Physiol 268:G189-99
Chicone, C C; Cai, Z S; King, P D et al. (1993) A parameter identification problem arising from a model of canalicular bile formation. J Math Biol 31:273-89
Cai, Z S; Burczynski, F J; Luxon, B A et al. (1992) On the design and interpretation of experiments to elucidate albumin-dependent hepatic uptake. Am J Physiol 262:G1127-37
Burczynski, F J; Moran, J B; Cai, Z S et al. (1990) Beta-lactoglobulin enhances the uptake of free palmitate by hepatocyte monolayers: the relative importance of diffusion and facilitated dissociation. Can J Physiol Pharmacol 68:201-6
Burczynski, F J; Cai, Z S; Moran, J B et al. (1989) Palmitate uptake by cultured hepatocytes: albumin binding and stagnant layer phenomena. Am J Physiol 257:G584-93
Moran, J B; Burczynski, F J; Cheek, R F et al. (1987) Protein binding of palmitate measured by transmembrane diffusion through polyethylene. Anal Biochem 167:394-9