Rapid inverse changes in α1B-and β2-adrenergic receptors and gene transcripts in acutely isolated rat liver cells

✍ Scribed by Edward J. N. Ishac; Eliane Lazar-Wesley; George Kunos

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 854 KB
• Volume: 152
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041520111

✦ Synopsis

In vitro incubation of hepatocytes acutely isolated from adult male rats leads to a rapid conversion of the adrenergic activation of glycogenolysis from an a , -receptor (a,AK) to a P,-receptor (p,AR) mediated response within 4 h. In order to understand the underlying mechanism, we examined time-dependent changes in al -and p,-adrenergic activation of glycogenolysis and second messenger systems, the cellular density and affinity of a l A R and P,AR, and the steady state levels of a,,AR and P,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 a , A R density, and a 70% decrease in a , ,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 P,AR density, and a twofold increase in P,AR mRNA levels. Exposure of cells to cycloheximide, 2 pM throughout the 4 h incubation, prevented the emergence of the phosphorylase response to isoproterenol and reduced P,AR densities, while the decrease in a1AR 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 CX,~AK mRNA and increase in P,AR mRNA levels and corresponding inverse changes in the synthesis of a,,AR and P,AR which account, at least in part, for the rapid conversion from a , -to P,-adrenergic glycogenolysis. Published 19YZ Wiley-l IS, Inc.