Molecular mechanism of inverse regulation of hepatic alpha-1 and beta-2-adrenergic receptors.
The adrenergic activation of glycogenolysis in the rat liver is converted from an alpha-1 to a beta-2-receptor mediated event in various conditions associated with cellular dedifferentiation. Short-term incubation of isolated hepatocytes in a serum-free medium results in a similar conversion of the adrenoceptor response, without concomitant changes in the density or affinity of alpha-1 or beta-receptor binding sites. This time-dependent conversion can be prevented or reversed by inhibitors of protein synthesis, by an endogenous inhibitor of phospholipase A2 (lipomodulin), or by removal of fatty acids from the medium through a lipid-trap. Conversely, activation of phospholipase A2 or addition of exogenous arachidonic acid to freshly isolated rat liver cells induces an acute conversion from alpha-1 to beta-type response, and the effect of the latter is prevented by the cyclooxygenase inhibitor, ibuprofen. It is proposed that reciprocal changes in alpha-1 and beta-2 receptor activity in rat liver cells are triggered by inverse changes in the coupling of the two receptors to their respective post-receptor pathways. These changes are mediated by a cyclooxygenase product generated through increased phospholipase A2 activity.
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D010641:Phenotype; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013997:Time Factors
D002395:Catecholamines; D008112:Liver Glycogen; D011942:Receptors, Adrenergic, alpha; D010741:Phospholipases A; D054467:Phospholipases A2