Phosphorylated derivatives of phloretin inhibit cyclic AMP accumulation in neuronal and glial tumor cells in culture.
The potencies of polyphloretin phosphate, di-4-phloretin phosphate, 4-phloretin phosphate and phloretin to inhibit the stimulation of cAMP accumulation by prostaglandins, isoproterenol and adenosine were studied in 2 clonal cell lines of CNS origin. The sequence of potency to inhibit PGE1 effects was the same in neuroblastoma (N4TG3) and human astrocytoma cells (1321N1): di-4-phloretin phosphate greater than polyphloretin phosphate greater than phloretin greater than 4-phloretin phosphate. The inhibition of PGE1 stimulated cAMP accumulation by the most prostaglandin-specific inhibitor di-4-phloretin phosphate was rapidly established after its addition, fully reversible after a 30 min preincubation period and independent of the presence of calcium. Kinetic studies of the inhibition of PGE1 effects by di-4-phloretin-phosphate suggest a different type of inhibition in 1321N1 and N4TG3 cells.
D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010693:Phloretin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000242:Cyclic AMP; D010693:Phloretin; D002118:Calcium