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Rapid inverse changes in α 1B ‐and β 2 ‐adrenergic receptors and gene transcripts in acutely isolated rat liver cells
Author(s) -
Ishac Edward J. N.,
LazarWesley Eliane,
Kunos George
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041520111
Subject(s) - endocrinology , medicine , glycogenolysis , glycogen phosphorylase , phenylephrine , receptor , incubation , forskolin , adrenergic receptor , glucagon , messenger rna , inositol , chemistry , biology , inositol phosphate , glycogen , biochemistry , gene , hormone , blood pressure
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.