Selective loss of hormonal induction of glutamate transport in primary cultures of hepatocytes from rats treated with CCl4.

A protocol for the mass isolation and successful cultivation of hepatocytes from the acinar zones 1 and 2 is described. The hepatocyte suspensions isolated from rats pretreated with CCl4 contain less than one-tenth of control levels of the perivenous marker enzyme glutamine synthetase, as judged by immunocytochemistry and enzyme activity excluding contamination by hepatocytes from zone 3. In culture these hepatocytes form morphologically and functionally intact monolayers. They synthesize urea and glucose at rates above those of controls, but are unable to produce glutamine. These results demonstrate the suitability of this culture system for the investigation of hepatic functions that are characteristic of cells from the periportal and midzonal part of the acinus. An interesting feature of these cultures is the failure of dexamethasone to induce the uptake of glutamate while the hormonal induction of the amino acid transport systems A and N and of tyrosine aminotransferase is not affected.