Effect of Insulin, Dexamethasone, and Glucagon on the Amino Acid Transport Ability of Four Rat Hepatoma Cell Lines and Rat Hepatocytes in Culture¹

The basal level and hormone-affected amino acid transport of rat hepatocytes and rat hepatoma cell lines H4-II-E-C3 (H35), HTC, McA-RH 8994 (8994), and McA-RH 7777 (7777) in culture were examined by investigating the amount of α-[1-¹⁴C]-aminoisobutyric acid (AIB) transported in 4 min and up to 4 hr at 37°. The substances tested were insulin, dexamethasone (DEX), glucagon, and dibutyryl cyclic adenosine 3′:5′-monophosphate. Without any hormone treatment cell line 7777 exhibited the maximum rate of AIB uptake, followed in order by cell lines HTC, 8994, H35, and hepatocytes. Insulin increased the uptake of AIB by hepatocytes as well as by all four of the hepatoma cell lines. DEX increased AIB transport in cell lines H-35 and 8994 and inhibited it in hepatocytes and hepatoma cell lines HTC and 7777. The effect of insulin and DEX was additive in cell lines H35 and 8994 and was antagonistic in hepatocytes and cell lines HTC and 7777. In contrast to their stimulatory effect on AIB transport in rat liver parenchymal cells, glucagon or dibutyryl cyclic adenosine 3′:5′-monophosphate had no effect on the transport system of any of these four cell lines. Furthermore, the potentiation of AIB transport by DEX, in response to glucagon or dibutyryl cyclic adenosine 3′:5′-monophosphate as seen in rat liver parenchymal cells, could not be observed in any of these four cell lines. Both actinomycin D and cycloheximide blocked any of the effects of insulin, DEX, or glucagon in all of these cell culture types. On the basis of these findings, we conclude that in spite of several similarities there is a marked heterogeneity in hormone responses among the various hepatoma cell lines, although each differs in some respect from the hepatocytes.