RT Journal Article
SR Electronic
T1 Glycine conjugation activity of benzoic acid and its acinar localization in the perfused rat liver.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 409
OP 416
VO 268
IS 1
A1 M Chiba
A1 K Poon
A1 J Hollands
A1 K S Pang
YR 1994
UL http://jpet.aspetjournals.org/content/268/1/409.abstract
AB Glycine conjugation activity toward benzoic acid (BA) was studied in the single-pass perfused rat liver preparation. The steady-state hepatic extraction ratio for the portal vein (PV) perfused liver (at 10 ml/min) was maximal (0.6) at input concentrations < 40 microM among perfusions varying from tracer to 700 microM. Glycine conjugation was the predominant pathway; the kinetic parameters estimated after appropriately correcting for plasma protein binding (KA = 8.37 x 10(3) M-1 and 1.9 sites) revealed a low Km (12 microM) and a moderately high Vmax (101 nmol.min-1.g-1 liver) system. Biliary excretion of BA and its glycine-conjugated metabolite, hippuric acid, was minimal. Under first-order conditions (input concentration < 2 microM), the method of HAPV and HAHV perfusion (trace [14C]benzoate delivered via the hepatic artery (HA) at 2 ml/min and blank perfusate via the portal vein (PV) or hepatic vein (HV) at 10 ml/min) was used to examine the localization of glycine conjugation activity toward BA. During steady state, a multiple indicator dose of 51Cr-labeled red blood cells (vascular marker), [58Co]EDTA (interstitial space marker, which behaves similar to labeled tracer sucrose) and 3H2O (cellular marker) was injected as a bolus into the HA. Values of the extraction ratio of BA for HAPV perfusion (0.59 +/- 0.09) were dramatically reduced during HAHV perfusion (0.061 +/- 0.033, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)