Studies on Responsiveness of Hepatoma Cells to Catecholamines I. Lack of β-Adrenergic Responsiveness in Rat Ascites Hepatoma AH13 Cells

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The β-adrenoceptor density and the activities of adenylate cyclase and cyclic AMP phosphodiesterase were examined to compare AH13 cells having lower β-adrenergic responsiveness with other rat ascites hepatoma cells and normal rat liver cells. Normal rat liver cells used were cultured for 24 hr after the collagenase digestion of liver. The density of binding sites of ³H-dihydroalprenolol in AH13 cell plasma membrane was very similar to the density in AH44 and normal liver cell membrane, but that in AH130 cell plasma membrane was about 10-fold greater than those in the other three cell lines. The activity of cyclic AMP phosphodiesterase was about 2.5 to 7-fold higher in hepatoma cells than in rat liver cells, but this enzyme activity of AH13 cells was not especially high among the hepatoma cells examined. The basal adenylate cyclase activity was lower in AH44 cells, but was higher in AH13 and AH130 cells than in rat liver cells. However, adenylate cyclase of AH13 cells was hardly activated by isoproterenol, while the enzyme of the other cells was activated 3 to 5-fold. On the other hand, adenylate cyclase of each cell line including AH13 was activated 4 to 14-fold by NaF. From these results, it is suggested that AH13 cells can hardly produce cyclic AMP by the β-adrenergic stimulation because of the disordered interaction of β-adrenoceptors with adenylate cyclase.