BETA-ADRENERGIC RECEPTORS AND ANGIOTENSINOGEN GENE-EXPRESSION IN MOUSE HEPATOMA-CELLS IN-VITRO

We have previously reported that addition of 8-bromocyclic AMP enhance s the stimulatory effect of dexamethasone on the expression of the ang otensinogen gene in mouse hepatoma cells in vitro. Isoproterenol is kn own to stimulate the synthesis of hepatic intracellular cyclic AMP via beta-adrenergic receptors. To study the possible effect of beta-adren ergic receptors on the expression of the angiotensinogen gene in mouse hepatoma cells, we transiently transfected them with a fusion gene wi th the 5'-flanking region of the angiotensinogen gene linked to a bact erial chloramphenicol acetyltransferase coding sequence as a reporter, pOCAT (ANG N-1498/+18). The addition of isoproterenol (10(-9) to 10(- 5) mol/L) alone had no stimulatory effect on the expression of pOCAT ( ANG N-1498/+18). In the presence of dexamethasone (10(-6) mol/L), howe ver, isoproterenol enhanced the stimulatory effect of the dexamethason e on the expression of pOCAT (ANG N-1498/+18). The enhancing effect of isoproterenol was inhibited by the presence of propranolol (beta(1)- and beta(2)-adrenergic receptor antagonist) and ICI 118,551 (beta(2)-a drenergic receptor antagonist) but not by the presence of atenolol (be ta(1)-adrenergic receptor antagonist). Furthermore, the addition of Rp -cAMP (an inhibitor of protein kinase A I and II) blocked the enhancin g effect of isoproterenol. These studies demonstrated that isoproteren ol enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells via a-adrenergic r eceptor and cyclic AMP-dependent protein kinase pathways. Our data may be important in understanding the molecular mechanism(s) of the stimu latory effect of catecholamines/ glucocorticoid-induced expression of the angiotensinogen gene in the liver.