A structure-activity study on the influence of phenolic compounds and bioflavonoids on rat renal prostaglandin synthetase

  • J. Baumann
  • F. v. Bruchhausen
  • G. Wurm
Article

Summary

The stimulating or inhibiting influences of 33 phenolic compounds on the prostaglandin synthetase of rat renal medulla were tested. Dihydroxyphenylcarbonic acids clearly proved to be activators of the prostaglandin synthetase. Dimethoxyphenylcarbonic acids were ineffective. Aminoethylphenols as well as p-substituted monohydroxybenzenes with a carbonic acid side chain were clear stimulators in contrast to their alkyl derivatives which are pronounced inhibitors. Among the tested bioflavonoids (+)-cyanidanol-3 and morin were inhibitors of the prostaglandin synthesis. Flavonoids with polar substitution in 3,5,7-position such as rutin on the other hand showed activating properties.

Key words

Prostaglandin biosynthesis Rat renal medulla Flavonoids Cofactor function of adrenalin Prostaglandin endoperoxide synthetase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahbfelt-Rønne, I.: In vitro stimulation of prostaglandin synthetase by methylxanthines. Prostaglandins 16, 711–724 (1978)Google Scholar
  2. Arturson, G., Jonsson, C. E.: Stimulation and inhibition of biosynthesis of prostaglandins in human skin by some hydroxyethylated rutosides. Prostaglandins 10, 941–948 (1975)Google Scholar
  3. Baumann, J., v. Bruchhausen, F.: (+)-Cyanidanol-3 as inhibitor of prostaglandin synthetase. Studies on renal medulla and liver of the rat in vitro and in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 85–87 (1979)Google Scholar
  4. Baumann, J., v. Bruchhausen, F., Wurm, G., Hänsel, R.: Dihydrocaffeic acid, a metabolite of bioflavonoids, as a cofactor of prostaglandin synthetase. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, R26 (1978)Google Scholar
  5. Booth, A. N., Murray, C. W., Jones, F. T., De Eds, F.: The metabolic fate of rutin and quercetin in the animal body. J. Biol. Chem. 223, 251–257 (1956)Google Scholar
  6. Christ, E. J., van Dorp, D. A.: Comparative aspects of prostaglandin biosynthesis in animal tissues. Adv. Biosc. 9, 35–38 (1973)Google Scholar
  7. Clark, W. M., MacKay, E. M.: The absorption and excretion of rutin and related flavonoid substances. J. Am. Med. Ass. 143, 1411–1415 (1950)Google Scholar
  8. Das, N. P., Griffiths, L. A.: Studies on flavonoid metabolism. Metabolism of (+)-catechin in the guinea pig. Biochem. J. 110, 449–456 (1968)Google Scholar
  9. Das, N. P., Sothy, S. P.: Studies on flavonoid metabolis. Biliary and urinary excretion of metabolites of (+)-[U-14C]-catechin. Biochem. J. 125, 417–423 (1971)Google Scholar
  10. Egan, R. W., Paxton, J., Kuchl Jr., F. A.: Mechanism for irreversible self-deactivation of prostaglandin synthetase. J. Biol. Chem. 251, 7329–7335 (1976)Google Scholar
  11. Flower, R. I., Cheung, H. S., Cushman, D. W.: Quantitative determination of prostaglandins and malonaldehyde formed by the oxygenase (prostaglandin synthetase) system of bovine seminal vesicle. Prostaglandins 4, 325–351 (1973)Google Scholar
  12. Griffiths, L. A., Smith, G. E.: Metabolism of myricetin and related compounds in the rat. Metabolic formation in vivo and by the intestinal microflora in vitro. Biochem. J. 130, 141–151 (1972)Google Scholar
  13. Horton, E. W., Thompson, C. J.: Thin layer chromatography and bioassay of prostaglandins in extracts of semen and tissues of the male reproductive tract. Br. J. Pharmacol. 22, 183–188 (1964)Google Scholar
  14. Ingerowski, R. M., Haux, F., v. Bruchhausen, F.: Decreased prostaglandin synthetase activity during kidney regeneration after folic acid or 2,4,5-triamino-6-styrylpyrimidine application. Naunyn-Schmiedeberg's Arch. Pharmacol. 298, 157–162 (1977)Google Scholar
  15. Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275 (1951)Google Scholar
  16. Miyamoto, T., Ogino, N., Yamamoto, S., Hayaishi, O.: Purification of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. J. Biol. Chem. 251, 2629–2636 (1976)Google Scholar
  17. Nugteren, D. H., Beerthuis, R. K., van Dorp, D. A.: The enzymic conversion of all-cis 8,11,14-eicosatrienoic acid into prostaglandin E1. Rec. Trav. Chim. 85, 405–419 (1966)Google Scholar
  18. Sih, C. J., Takeguchi, C., Foss, P.: Mechanism of prostaglandin biosynthesis. III. Catecholamines and serotonin as coenzymes. J. Am. Chem. Soc. 92, 7, 6670 (1970)Google Scholar
  19. Smith, W. L., Lands, W. E. M.: Stimulation and blockade of prostaglandin biosynthesis. J. Biol. Chem. 246, 6700–6702 (1971)Google Scholar
  20. Tai, H. H., Tai, C. L., Hollander, C. S.: Biosynthesis of prostaglandins in rabbit kidney medulla. Properties of prostaglandin synthase. Biochem. J. 154, 257–264 (1976)Google Scholar
  21. Takacs, Ö, Benkö, S., Varga, L., Antal, A., Gabor, M.: Metabolisms of flavonoids. Angiologica 9, 175–180 (43–48) (1972)Google Scholar
  22. Takeguchi, C., Kohno, E., Sih, C. J.: Mechanism of prostaglandin biosynthesis. I. Characterization and assay of bovine prostaglandin synthetase. Biochemistry 10, 2372–2376 (1971)Google Scholar
  23. Tan, W. C., Privett, O. S.: Analysis of prostaglandins in rat vesicular glands. Lipids 7, 622–624 (1972)Google Scholar
  24. Tomlinson, R. V., Ringold, H. J., Qureshi, M. C., Forchielli, E.: Relationship between inhibition of prostaglandin synthesis and drug efficacy: Support for the current theory on mode of action of aspirin-like drugs. Biochem. Biophys. Res. Commun. 46, 552–559 (1972)Google Scholar
  25. Yanagi, Y., Komatsu, T.: Inhibition of prostaglandin biosynthesis by BY SL-573. Biochem. Pharmacol. 25, 930–941 (1976)Google Scholar
  26. Yoshimoto, A., Ito, H., Tomita, K.: Cofactor requirements of the enzyme synthesizing prostaglandin in bovine seminal vesicles. J. Biochem. (Tokyo) 68, 487–499 (1970)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • J. Baumann
    • 1
  • F. v. Bruchhausen
    • 1
  • G. Wurm
    • 2
  1. 1.Pharmakologisches Institut der Freien Universität BerlinBerlin 33
  2. 2.Institut für Pharmazie der Freien Universität BerlinBerlin 33

Personalised recommendations