Inverse reciprocal regulation of alpha 1- and beta 2-adrenoceptors in the rat liver: possible mechanism.
Reciprocal changes in alpha- and beta-receptor responses occur in a number of in vivo as well as in vitro conditions. Incubation of isolated rat liver cells in a serum-free buffer results in the conversion of the adrenergic activation of glycogenolysis from an alpha 1 to a beta-receptor mediated response within 4 h. The decrease in the alpha 1-adrenergic response and the simultaneous emergence of a beta-adrenergic response are selective with regards to the effects of other glycogenolytic hormones and are not accompanied by changes in the density or affinity of alpha 1 or beta-receptor binding sites. Lipomodulin, an endogenous inhibitor of membrane phospholipase A2, reverses the receptor response in 4 h cells from beta to alpha, whereas lipomodulin antibody, or melittin, a phospholipase A2 activator, have opposite effects in freshly isolated cells. The time-dependent conversion of the adrenoceptor response is prevented by the presence of indomethacin or inhibitors of protein or mRNA synthesis, and is accelerated by a serine protease inhibitor. These findings are interpreted to indicate that changes in membrane phospholipase A2 activity are involved in the conversion of the adrenergic receptor response in isolated rat liver cells, by influencing the coupling of alpha 1 and beta-receptors to postreceptor pathways in an inverse, reciprocal manner. The activation of this mechanism requires a protein factor(s), whose cellular levels are controlled by a balance between protein synthetic and proteolytic activities. The possibility that this phospholipase effect is mediated by a cyclooxygenase product is under study.
Kunos
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Ishac
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D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D017302:Annexins; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
D017302:Annexins; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D008112:Liver Glycogen; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C030958:lipomodulin; D014667:Vasopressins; D015117:5,8,11,14-Eicosatetraynoic Acid; D003609:Dactinomycin; D010656:Phenylephrine; D005934:Glucagon; D003513:Cycloheximide; D010741:Phospholipases A; D054467:Phospholipases A2; D007545:Isoproterenol