Hepatic cyclic AMP generation and ornithine decarboxylase induction by glucagon and beta adrenergic agonists.
The relationship of hepatic ornithine decarboxylase (ODC) activity to cyclic AMP levels and nutritional status was studied in the pre-weanling rat. Previous studies demonstrated that 2 hr without food causes a loss of hepatic ODC induction after glucagon or catecholamine injection. Isoproterenol or glucagon administration produced increased hepatic cyclic AMP and tyrosine aminotransferase activity which were not prevented by nutritional deprivation. Blockade of hepatic beta 2 receptors by the selective antagonist ICI 118,551 prevented increased cAMP levels and ODC activity after isoproterenol administration. Blockade of beta 1 receptors by atenolol did not prevent increased cAMP levels or ODC induction by isoproterenol although it did block activation of cardiac ODC. The phosphodiesterase inhibitor RO20-1724 increased hepatic cAMP levels as well as ODC and TAT activities, although the increase in ODC activity was attenuated by nutritional deprivation. RO20-1724 also potentiated the induction of hepatic ODC after glucagon or isoproterenol administration. Administration of 8-bromo cAMP elevated hepatic ODC activity regardless of nutritional status but also elevated serum levels of growth hormone and corticosterone. Hepatic ODC induction by glucagon or beta 2 agonists can be dissociated from changes in cAMP levels during nutritional deprivation.
Evoniuk
G
G
Kuhn
C M
CM
Schanberg
S M
SM
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005508:Food Deprivation; D005934:Glucagon / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014444:Tyrosine Transaminase / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000628:Aminophylline; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003994:Bucladesine; D013006:Growth Hormone; D005934:Glucagon; D000242:Cyclic AMP; D014444:Tyrosine Transaminase; D009955:Ornithine Decarboxylase; D007545:Isoproterenol; D003345:Corticosterone