Reduced transport of bilirubin and asialoorosomucoid in regenerating rat liver is a microtubule-independent event
✍ Scribed by Yacov R. Stollman; Dr. Lorenz Theilmann; Richard J. Stockert; Allan W. Wolkoff
- Book ID
- 102851755
- Publisher
- John Wiley and Sons
- Year
- 1985
- Tongue
- English
- Weight
- 612 KB
- Volume
- 5
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
In previous studies, we found that uptake of bilirubin and asialoorosomucoid is depressed in regenerating rat liver. To determine what role the hepatic cytoskeleton plays in this modulation of uptake, animals were treated with colchicine, an inhibitor of microtubular polymerization. Normal unoperated rats or rats following two-thirds hepatectomy or sham surgery were injected with colchicine, lumicolchicine (60 wg per 100 gm of body weight, i.p.) or normal saline. Lumicolchicine, an analog of colchicine, has no effect on microtubules and was used as a control. At 12 h r after surgery, sham-operated and unoperated animals received a second equal dose. Partially hepatectomized animals received one-third the initial dose. At 24 hr after surgery, livers were perfused in situ and single-pass multiple indicator dilution studies were performed. Colchicine as compared to lumicolchicine pretreatment reduced apparent influx of bilirubin and asialoorosomucoid in regenerating liver by 50% but had no effect in liver from normal or sham-operated rats. Analysis of indicator dilution curves revealed that reduced influx in colchicine-treated liver was attributable to an increased vascular volume of distribution. These results suggest that microtubules may play a role in maintenance of normal hepatic vascular architecture during regeneration. Lack of effect of colchicine on modulation of bilirubin and asialoorosomucoid uptake during regeneration suggests that other, as yet unknown, factors result in down-regulation of the specific hepatocellular transport systems for these two ligands.
Hepatocyte uptake of bilirubin and asialoorosomucoid from the circulation is rapid and efficient (1-3). These compounds are representative of two classes of ligands (i.e., organic anions and asialoglycoproteins) which have independent uptake mechanisms although each has carrier-mediated kinetics (4). Asialoglycoproteins bind to a liver cell surface receptor and undergo receptor-mediated endocytosis (3). Endocytosis is not a feature of uptake of organic anions, which may interact with a specific surface membrane protein( s) prior to translocation into cytosol (5).
The normal rat hepatocyte divides approximately once per year (6). However, following two-thirds hepatectomy,