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Phosphorylated derivatives of phloretin inhibit cyclic AMP accumulation in neuronal and glial tumor cells in culture

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Summary

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 > polyphloretin phosphate > phloretin >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.

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Abbreviations

PPP:

polyphloretin phosphate

MPP:

4-phloretin phosphate

DPP:

di-4-phloretin phosphate

IBMX:

3-isobutyl-methylxanthine

TCA:

trichloroacetic acid

HEPES:

N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid

EGTA:

Ethylenglycol-bis (β-amino ethylether) N,N′-tetraacetic acid

PGE1 :

Prostaglandin E1

125J-TME ScAMP:

(125J) 2′-O-succinyl cyclic AMP tyrosine methyl ester

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  1. R. Ortmann

    Present address: Research Department, Pharmaceutical Division, Ciba-Geigy Ltd., Basle, Switzerland

Authors and Affiliations

  1. Pharmakologisches Institut der Universität Freiburg, Hermann-Herder-Strasse 5, D-7800, Freiburg, Federal Republic of Germany

    R. Ortmann, D. Nutto & R. Jackisch

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  1. R. Ortmann
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  2. D. Nutto
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  3. R. Jackisch
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Ortmann, R., Nutto, D. & Jackisch, R. Phosphorylated derivatives of phloretin inhibit cyclic AMP accumulation in neuronal and glial tumor cells in culture. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 233–240 (1978). https://doi.org/10.1007/BF00498816

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  • DOI: https://doi.org/10.1007/BF00498816

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