An arachidonate metabolite is involved in the conversion from alpha 1- to beta-adrenergic glycogenolysis in isolated rat liver cells.
In vitro incubation of isolated rat liver cells in a serum-free buffer leads to the suppression of the glycogenolytic effect of phenylephrine and the simultaneous emergence of a glycogenolytic response to isoproterenol within 4 hr. This time-dependent conversion of the adrenergic receptor response from alpha 1 to beta type is prevented by the presence in the incubation medium of 0.5% fatty-acid-free, but not regular, bovine serum albumin. A 20-min exposure of freshly isolated liver cells to arachidonic acid (10 micrograms/ml), but not to stearic or palmitic acid, causes an acute shift in the receptor response from alpha 1 to mixed alpha 1/beta type, similar in direction to that seen after prolonged incubation of the cells. This effect of arachidonic acid is prevented by 0.2 microM ibuprofen but not by the same concentration of nordihydroguaiaretic acid. Ibuprofen (1 microM) or indomethacin (1 microM) also inhibits the time-dependent shift in the receptor response. Actinomycin D inhibits the change in receptor response that is caused by prolonged incubation but not the change that is caused by exogenous arachidonic acid. It is proposed that the time-dependent conversion from alpha 1- to beta-adrenergic receptor-mediated glycogenolysis in isolated rat liver cells is related to a parallel increase in the phospholipase-mediated release of arachidonic acid and the subsequent formation of a key cyclooxygenase metabolite. A protein factor appears to be involved in the regulation of the release of arachidonic acid but not in the action of its metabolite. A possible mechanism by which this metabolite may regulate inverse changes in the coupling of alpha 1- and beta-receptors to postreceptor pathways is discussed.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009637:Masoprocol; D010656:Phenylephrine / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D002396:Catechols; D005227:Fatty Acids; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D003609:Dactinomycin; D010656:Phenylephrine; D016718:Arachidonic Acid; D009637:Masoprocol; D006003:Glycogen; D011433:Propranolol; D010741:Phospholipases A; D007545:Isoproterenol; D007052:Ibuprofen; D011224:Prazosin; D004837:Epinephrine