Induction of glycogenolysis in cultured Ewing's sarcoma cells by dopamine and beta-adrenergic agonists.
This study describes hormonal regulation of glycogen metabolism in Ewing's sarcoma cells. 3H-Glycogen synthesized in cultured Ewing's sarcoma WE-68 cells from 3H-glucose was hydrolyzed in a concentration-dependent manner by various catecholamines. The order of potency for the glycogenolytic effects of catecholamines was isoproterenol greater than or equal to dopamine greater than norepinephrine greater than epinephrine. The concentrations giving half-maximal effectiveness (EC50) were about 2 x 10(-8) M, 3 x 10(-8) M, 8 x 10(-8) M, and 5 x 10(-7) M for isoproterenol, dopamine, norepinephrine, and epinephrine, respectively. Higher concentrations of each of the catecholamines were necessary to elicit EC50 stimulation of cyclic AMP production in Ewing's sarcoma cells. Glycogenolysis induced by dopamine was blocked by chlorpromazine, a dopamine D1-receptor antagonist, but not by haloperidol, a dopamine D2-receptor antagonist. The glycogenolytic action of norepinephrine was markedly reduced by propranolol, a beta-adrenoreceptor antagonist, and was not affected by yohimbine, an alpha-adrenoreceptor antagonist. In addition, chlorpromazine also antagonized the glycogenolytic response to norepinephrine. Dibutyryl cyclic AMP, 3-isobutyl-1-methylxanthine, and the diterpene forskolin were also found to induce 3H-glycogen hydrolysis. Our data indicate that catecholamines exert their glycogenolytic effects in Ewing's sarcoma cells by stimulation of cyclic AMP formation via beta-adrenergic receptors and dopamine D1-receptors.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006003:Glycogen / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012512:Sarcoma, Ewing / Q000378:metabolism*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D006003:Glycogen; D000242:Cyclic AMP; D006220:Haloperidol; D002746:Chlorpromazine; D004298:Dopamine; D009638:Norepinephrine