Rapid inverse changes in α 1B ‐and β 2 ‐adrenergic receptors and gene transcripts in acutely isolated rat liver cells

In vitro incubation of hepatocytes acutely isolated from adult male rats leads to a rapid conversion of the adrenergic activation of glycogenolysis from an α 1 ‐receptor (α 1 AR) to a β 2 ‐receptor (β 2 AR) mediated response within 4 h. In order to understand the underlying mechanism, we examined time‐dependent changes in α 1 ‐ and β 2 ‐adrenergic activation of glycogenolysis and second messenger systems, the cellular density and affinity of α 1 AR and β 2 AR, and the steady state levels of α 1B AR and β 2 AR mRNAs. Incubation of hepatocytes for 4 h resulted in a decrease in phosphorylase activation and inositol 1,4,5 trisphosphate accumulation in response to phenylephrine, a 40% decrease in α 1 AR density, and a 70% decrease in α 1B AR mRNA levels. Incubation of hepatocytes for 4 h also resulted in the emergence of a phosphorylase response to isoproterenol, an increase in isoproterenol‐induced but not in glucagon‐ or forskolin‐induced cAMP accumulation, no significant change in β 2 AR density, and a twofold increase in β 2 AR mRNA levels. Exposure of cells to cycloheximide, 2 μM throughout the 4 h incubation, prevented the emergence of the phosphorylase response to isoproterenol and reduced β 2 AR densities, while the decrease in α 1 AR density was not affected and the decrease in phosphorylase activation by phenylephrine was attenuated. The results indicate that dissociation of rat liver cells triggers a rapidly developing decrease in α 1B AR mRNA and increase in β 2 AR mRNA levels and corresponding inverse changes in the synthesis of α 1B AR and β 2 AR which account, at least in part, for the rapid conversion from α 1 ‐ to β 2 ‐adrenergic glycogenolysis. © 1992 Wiley‐Liss, Inc.