Hepatocyte beta-adrenergic responsiveness and guanine nucleotide-binding regulatory proteins.
Hepatocytes isolated from hypothyroid, adrenalectomized, or partially hepatectomized rats display an enhanced beta-adrenergic responsiveness as compared with cells from control animals. The enhanced beta-adrenergic responsiveness is evidenced by both increased ureagenesis and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in response to isoproterenol. The role of stimulatory guanine nucleotide-binding protein (Gs) and inhibitory guanine nucleotide-binding protein (Gi) in the enhanced responsiveness was studied. It was observed, contrary to what would have been anticipated, that the level of Gs [as reflected by cholera toxin-catalyzed ADP ribosylation, 5'-guanosine gamma-thiotriphosphate (GTP gamma S)-stimulated adenylate cyclase activity, and a functional reconstitution assay] was decreased in liver membranes from adrenalectomized and partially hepatectomized rats as compared with the controls. Furthermore, the level of Gi was increased in these conditions as reflected by pertussis toxin-catalyzed ADP ribosylation. The data suggest that changes in beta-adrenergic receptor levels rather than the levels of guanine nucleotide-binding (G) regulatory proteins predominate in regulation of hepatic beta-adrenergic responses by hypothyroidism, adrenalectomy, or partial hepatectomy.
García-Sáinz
J A
JA
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City.
Huerta-Bahena
M E
ME
Malbon
C C
CC
D000262:Adenylyl Cyclases / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006498:Hepatectomy; D007037:Hypothyroidism / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008115:Liver Regeneration; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values
D011943:Receptors, Adrenergic, beta; D002772:Cholera Toxin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol