Cell-Density-Dependent Expression of the α_2-Adrenergic Response by Epidermal Growth Factor (EGF) in Primary Cultures of Adult Rat Hepatocytes

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Effects of epidermal growth factor (EGF) on the expression of α_2-adrenergic responses were examined in primary cultures of adult rat hepatocytes. The α_2-responses were assessed by the inhibition of the rate of forskolin-stimulated cAMP formation by the selective α_2-adrenergic agonists, oxymetazoline and UK-14304. Hepatocytes cultured with EGF (20 ng/ml) at a high cell density (1.0×10^5/cm^2) showed almost no response to the α_2-adrenergic agonists, oxymetazoline and UK-14304 (1-100 μM). In contrast, when cultured at a low cell density (3.3×10^4 cells/cm^2)with EGF, forskolin-stimulated cAMP production was inhibited by oxymetazoline and UK-14304 in a dose-dependent manner. The α_2-response was blocked by the α_2-antagonist yohimbine (10 μM). It was also reversed by treatment of hepatocytes with pertussis toxin (100 ng/ml). In addition, the effects of EGF on the appearance of α_2-responses were almost completely inhibited by treatment of the hepatocytes with genistein (10 μM) or cytochalasin B (10 μM). The α_2-response was abolished when cycloheximide (5 μM) was added to the cultures. These results demonstrate that when cultured at a low cell density with EGF, adult rat hepatocytes acquire a significant α_2-adrenergic response. The expression of this α_2-response is associated with de novo protein synthesis.
公益社団法人日本薬学会の論文
1996-04-15