Beta-adrenergic agonist- and prostaglandin-mediated regulation of cAMP levels in Ewing's sarcoma cells in culture.

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.