Effects of chronic propranolol treatment on hepatic adenylate cyclase system in the rat.
The biochemical aspects of hepatic beta-adrenergic receptors and adenylate cyclase activity in male adult rats were examined during chronic treatment of a beta-adrenergic antagonist, propranolol. The blockade of beta-adrenergic nervous systems for 7 to 10 days produced a considerable elevation of basal, glucagon, sodium fluoride, and 5'-guanylylimidodiphosphate, Gpp (NH)p-stimulated enzyme activity with a negligible response to a beta-adrenergic agonist, isoproterenol. There was no alteration in the density or the affinity of beta-adrenergic receptors for the agonist during the treatment. Guanine nucleotides have failed to induce a transformation of the higher affinity to the lower affinity state of beta-adrenergic receptors of the hepatic membrane derived either from control or the propranolol-treated animals. The activity of stimulatory guanine nucleotide regulatory proteins (Ns) in the enzyme, assessed by ADP-ribosylation was also not altered by the antagonist. These results suggest that the mechanism of the observed sensitization of adenylate cyclase induced by chronic beta-adrenergic blockade involves facilitation of Ns interaction with the catalytic subunit of the enzyme with no change in the beta-adrenergic receptor functions.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D005934:Glucagon / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000502:physiology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D011412:Propanolamines / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D008112:Liver Glycogen; D011412:Propanolamines; D006165:Guanylyl Imidodiphosphate; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D005934:Glucagon; D011433:Propranolol; D000262:Adenylyl Cyclases; C033394:CGP 12177