Heterogeneous expression of UDP-glucuronosyltransferases in periportal and perivenous hepatocytes.

Hepatocytes in the afferent (periportal) and efferent (perivenous) acinar zones have different morphological and biochemical characteristics [ I ] . Periportal hepatocytes have a greater capacity for gluconeogenesis and urea synthesis, and a lower capacity for lipogenesis and glutamine formation compared to perivenous hepatocytes [I]. The pathways of detoxification such as monooxygenation and sulphation are also thought to be heterogeneously distributed across the hepatic acinus. Cytochrome P-450s have been localised to either the periportal or perivenous zone depending on the class of substrate [ I ] . The UDPglucuronosyltransferases (UGTs) are microsomal enzymes and catalyse the conjugation of the sugar acid moiety of glucuronic acid with many endogenous and exogenous compounds.GIucuronidation takes place in a variety of tissues but predominantly the liver. Human UGT activity towards 4methylumbelliferone is mainly located in the perivenous zone of the liver acinus [2]. There is little information on the acinar zonation of different UGT isoforms. We therefore determined the activity of UGT isoenzymes towards bilirubin and 1 -naphthol substrates in hepatocytes isolated from the periportal and perivenous zones of male and female rats. Hepatocytes were isolated from either the periportal or perivenoous zones of the liver by the digitonin-collagenase perfusion technique with minor modifications [3]. Microsomal fractions were then prepared by homogenising cells in 250mM sucrose/SmM Hepes and centrifuging at 8000 g for 20s The supernatents were removed and centrifuged at 105,000 g for 30minutes. The pellet was resuspended in 250 mM sucrose / 5mM Hepes (pH 7.4) and stored at