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Vol. 27, Issue 3, 336-341, March 1999

Lack of Zonal Uptake of Estrone Sulfate in Enriched Periportal and Perivenous Isolated Rat Hepatocytes

Eugene Tan, Rommel G. Tirona, and K. Sandy Pang

Department of Pharmaceutical Sciences, Faculty of Pharmacy (E.T, R.G.T, K.S.P) and Department of Pharmacology, Faculty of Medicine (K.S.P), University of Toronto, Toronto, Ontario, Canada

The zonal uptake of estrone sulfate (E1S; 1 to 400 µM) was investigated in periportal and perivenous rat hepatocytes and cells isolated from whole liver (regular hepatocytes). Transport of E1S by periportal, perivenous, and regular hepatocytes was described by saturable (Kms of 24 to 26 µM and Vmaxs of 1.8 nmol/min/mg protein) and nonsaturable components (2.5 to 3.2 µl/min/mg protein) that were not different among the zonal regions (p > .05, ANOVA). These kinetic constants represented pooled values for the entire complement of transporters for E1S, including two known transporters of E1S: Ntcp, Na+-taurocholate cotransporting polypeptide, and oatp1, the organic anion transporting polypeptide cloned from rat liver. Uptake of E1S was significantly reduced by estradiol 17beta -glucuronide (50 µM) and bumetanide (200 µM), and was inhibited strongly and competitively by pregnenolone sulfate with an inhibition constant of 6.7 µM. Further segregation of the kinetic constants as the sodium-dependent and -independent systems was achieved through simultaneous fitting of data obtained in the presence and absence of sodium from parallel hepatocytic uptake studies. For the periportal, perivenous, and regular hepatocytes, two saturable systems: a sodium-dependent transport system, characterized by similar Vmaxs (1.1 to 1.4 nmol/min/mg protein) and Kms (49 to 55 µM), a sodium-independent transport system of comparable Vmaxs (0.70 to 0.84 nmol/min/mg protein) and Kms (16 to 22 µM), and a linear clearance of 1.7 to 2.7 µl/min/mg protein (ANOVA, p > .05) were obtained. The data suggest that hepatic uptake of E1S involved sodium-dependent and -independent transporter systems. No heterogeneity in transport was observed.

Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.