title: Beta-adrenergic agonist- and prostaglandin-mediated regulation of cAMP levels in Ewing's sarcoma cells in culture.
abstract: This is the first report demonstrating hormonal control of cAMP levels in Ewing's sarcoma cells. Two classes of hormones, beta-adrenergic agonists and prostaglandins stimulate cAMP production in cultured Ewing's sarcoma cells. The efficacy order for beta-adrenergic agonists is (-)-isoprenaline greater than or equal to (-)-noradrenaline greater than or equal to (-)-adrenaline much greater than (-)-phenylephrine. The stimulatory effect of (-)-noradrenaline is antagonized by beta 1-selective metoprolol and also by beta 2-selective ICI 118,551. The efficacy order for prostaglandins (PG) is PGE1 greater than PGI2 greater than PGE2 much greater than PGF2 alpha; 6-keto PGF1 alpha and PGD2 do not influence cAMP levels in Ewing's sarcoma cells. Cultures pretreated with PGE2 are less responsive to a second challenge with PGE2 but their response to (-)-isoprenaline is unimpaired. Similarly, pretreatment with (-)-isoprenaline induces homologous desensitization to (-)-isoprenaline and has no effect on the PGE2-stimulated increase in cAMP. We conclude that these cells provide an ideal model for the study of the initial steps of beta-adrenergic and prostaglandin action in Ewing's sarcoma.
mesh_terms: D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D012512:Sarcoma, Ewing / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011453:Prostaglandins; D011458:Prostaglandins E; D010656:Phenylephrine; C026777:ICI 118551; D000242:Cyclic AMP; D015232:Dinoprostone; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine