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Intrahepatic cholestasis as a canalicular motility disorder. Evidence using cytochalasin
Abstract:
A rich network of actin-containing microfilaments are associated with the plasma membrane of the liver cells. These filaments are especially numerous in the pericanalicular region. Recently, active contractions of bile canaliculi have been observed in normal coupled isolated hepatocytes. In this report, we document that this motility behavior is abolished by cytochalasins B and D. Other cytoplasmic contractile movements are also reduced or lost after a brief initial period of enhanced surface activity with the formation of zeiotic blebs. The lack of contractile activity of bile canaliculi is accompanied by the gradual dilation of canalicular lumina. Since there is overwhelming evidence that the functional effects of the cytochalasins on cell motility are due to their effects on actin filaments, we propose that the altered canalicular contractility observed is due to the effects of cytochalasin on pericanalicular actin filaments. If bile canalicular contractility is a requirement for normal bile flow, then interference with this mechanism may be a factor in the pathogenesis of some types of intrahepatic cholestasis.
Insights
Cytochalasin B and D disrupt actin filaments in liver cells, abolishing bile canaliculi contractions. This motility loss may contribute to intrahepatic cholestasis by impairing bile flow.
Area of Science:
- Hepatology
- Cell Biology
- Biochemistry
Background:
- Liver cells possess actin microfilaments, particularly around bile canaliculi.
- Recent observations show active contractions in isolated, coupled hepatocytes.
Purpose of the Study:
- To investigate the effect of cytochalasins on bile canaliculi contractility.
- To explore the role of actin filaments in hepatocyte motility and bile flow.
Main Methods:
- Treatment of isolated hepatocytes with cytochalasins B and D.
- Observation of bile canaliculi motility and structure.
Main Results:
- Cytochalasins B and D abolished bile canaliculi contractions.
- Cytoplasmic contractile movements were reduced, with initial zeiotic bleb formation.
- Loss of contractility led to gradual dilation of canalicular lumina.
Conclusions:
- Cytochalasin-induced loss of bile canaliculi contractility is attributed to effects on pericanalicular actin filaments.
- Impaired bile canaliculi contractility may play a role in the pathogenesis of intrahepatic cholestasis.