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. 1976 Oct;58(2):193–199. doi: 10.1111/j.1476-5381.1976.tb10396.x

Stimulation of prostaglandin biosynthesis by drugs: effects in vitro of some drugs affecting gut function.

H O Collier, W J McDonald-Gibson, S A Saeed
PMCID: PMC1667316  PMID: 824000

Abstract

Low concentrations of several emetic, purgative or irritant drugs in the absence of added co-factors stimulated conversion of arachidonic acid to prostaglandin E2 and F2alpha by prostaglandin synthetase extracted from bull seminal vesicles (BSV prostaglandin synthetase). Their effect was dependent on concentration and time. Stimulation of BSV prostaglandin synthetase by apomorphine, aloes, tyramine or zingerone was increased several-fold by addition of reduced glutathione to the incubation medium, whereas hydroquinone, a phenolic co-factor of prostaglandin synthetase caused slight depression. From this finding and from the observation that many of the stimulant drugs possess a phenolic group, whereas their inactive relatives lack such a group, it is suggested that these stimulant drugs act as co-factors for prostaglandin synthetase in place of hydroquinone. Aloes, tyramine, ethanol and quipazine also produced a dose-related increase in resting tone of the isolated fundus of the rat stomach. This increase occurred at concentrations comparable to those effective in stimulating BSV prostaglandin synthetase, and was abolished by acetylsalicylate. These findings support the view that certain drugs exert some of their pharmacological effects by stimulating prostaglandin synthetase.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett A., Friedmann C. A., Vane J. R. Release of prostaglandin E-1 from the rat stomach. Nature. 1967 Dec 2;216(5118):873–876. doi: 10.1038/216873a0. [DOI] [PubMed] [Google Scholar]
  2. Butt A. A., Collier H. O., Gardiner P. J., Saeed S. A. Proceedings: Effects on prostaglandin biosynthesis of drugs affecting gastrointestinal function. Gut. 1974 Apr;15(4):344–344. [PubMed] [Google Scholar]
  3. Coceani F., Pace-Asciak C., Volta F., Wolfe L. S. Effect of nerve stimulation on prostaglandin formation and release from the rat stomach. Am J Physiol. 1967 Oct;213(4):1056–1064. doi: 10.1152/ajplegacy.1967.213.4.1056. [DOI] [PubMed] [Google Scholar]
  4. Collier H. O., McDonald-Gibson W. J., Saeed S. A. Apomorphine and morphine stimulate prostaglandin biosynthesis. Nature. 1974 Nov 1;252(5478):56–58. doi: 10.1038/252056a0. [DOI] [PubMed] [Google Scholar]
  5. Collier H. O., McDonald-Gibson W. J., Saeed S. A. Letter: Stimulation of prostaglandin biosynthesis by capsaicin, ethanol, and tyramine. Lancet. 1975 Mar 22;1(7908):702–702. doi: 10.1016/s0140-6736(75)91818-8. [DOI] [PubMed] [Google Scholar]
  6. Eckenfels A., Vane J. R. Prostaglandins, oxygen tension and smooth muscle tone. Br J Pharmacol. 1972 Jul;45(3):451–462. doi: 10.1111/j.1476-5381.1972.tb08101.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GREEN K., SAMUELSSON B. PROSTAGLANDINS AND RELATED FACTORS: XIX. THIN-LAYER CHROMATOGRAPHY OF PROSTAGLANDINS. J Lipid Res. 1964 Jan;5:117–120. [PubMed] [Google Scholar]
  8. Hannington E. Preliminary report on tyramine headache. Br Med J. 1967 May 27;2(5551):550–551. doi: 10.1136/bmj.2.5551.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Herman A. G., Vane J. R. Endotoxin and production of prostaglandins by the isolated rabbit jejunum. Influence of indomethacin. Arch Int Pharmacodyn Ther. 1975 Feb;213(2):328–329. [PubMed] [Google Scholar]
  10. Horton E. W., Main I. H., Thompson C. J., Wright P. M. Effect of orally administered prostaglandin E1 on gastric secretion and gastrointestinal motility in man. Gut. 1968 Dec;9(6):655–658. doi: 10.1136/gut.9.6.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Karppanen H., Puurunen J. Ethanol, indomethacin and gastric acid secretion in the rat. Eur J Pharmacol. 1976 Jan;35(1):221–223. doi: 10.1016/0014-2999(76)90320-4. [DOI] [PubMed] [Google Scholar]
  12. Main I. H., Whittle B. J. Potency and selectivity of methyl analogues of prostaglandin E2 on rat gastrointestinal function. Br J Pharmacol. 1975 Jul;54(3):309–317. doi: 10.1111/j.1476-5381.1975.tb07570.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Matuchansky C., Bernier J. J. Effect of prostaglandin E 1 on glucose, water, and electrolyte absorption in the human jejunum. Gastroenterology. 1973 Jun;64(6):1111–1118. [PubMed] [Google Scholar]
  14. Milton-Thompson G. J., Cummings J. H., Newman A., Billings J. A., Misiewicz J. J. Colonic and small intestinal response to intravenous prostaglandin F2 alpha and E2 in man. Gut. 1975 Jan;16(1):42–46. doi: 10.1136/gut.16.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Misiewicz J. J., Waller S. L., Kiley N. Effect of oral prostaglandin E1 on intestinal transit in man. Lancet. 1969 Mar 29;1(7596):648–651. doi: 10.1016/s0140-6736(69)92012-1. [DOI] [PubMed] [Google Scholar]
  16. Pace-Asciak C. Prostaglandin synthetase activity in the rat stomach fundus. Activation by L-norepinephrine and related compounds. Biochim Biophys Acta. 1972 Sep 7;280(1):161–171. doi: 10.1016/0005-2760(72)90221-4. [DOI] [PubMed] [Google Scholar]
  17. Pace-Asciak C., Wolfe L. S. Biosynthesis of prostaglandins E2 and F2-alpha from tritium-labelled arachidonic acid by rat stomach homogenates. Biochim Biophys Acta. 1970 Dec 15;218(3):539–542. doi: 10.1016/0005-2760(70)90017-2. [DOI] [PubMed] [Google Scholar]
  18. Robinson D. R., Smith H., McGuire M. B., Levine L. Prostaglandin synthesis by rheumatoid synovium and its stimulation by colchicine. Prostaglandins. 1975 Jul;10(1):67–85. doi: 10.1016/0090-6980(75)90094-5. [DOI] [PubMed] [Google Scholar]
  19. Rodríguez R., Pardo E. G. Quipazine, a new type of antidepressant agent. Psychopharmacologia. 1971;21(1):89–100. doi: 10.1007/BF00404000. [DOI] [PubMed] [Google Scholar]
  20. Sandler M., Youdim M. B., Hanington E. A phenylethylamine oxidising defect in migraine. Nature. 1974 Jul 26;250(464):335–337. doi: 10.1038/250335a0. [DOI] [PubMed] [Google Scholar]
  21. Sih C. J., Takeguchi C., Foss P. Mechanism of prostaglandin biosynthesis. 3. Catecholamines and serotonin as coenzymes. J Am Chem Soc. 1970 Nov 4;92(22):6670–6670. doi: 10.1021/ja00725a064. [DOI] [PubMed] [Google Scholar]
  22. Smith W. L., Lands W. E. Stimulation and blockade of prostaglandin biosynthesis. J Biol Chem. 1971 Nov;246(21):6700–6702. [PubMed] [Google Scholar]
  23. THOMAS L. The physiological disturbances produced by endotoxins. Annu Rev Physiol. 1954;16:467–490. doi: 10.1146/annurev.ph.16.030154.002343. [DOI] [PubMed] [Google Scholar]
  24. Takeguchi C., Kono E., Sih C. J. Mechanism of prostaglandin biosynthesis. I. Characterization and assay of bovine prostaglandin synthetase. Biochemistry. 1971 Jun 8;10(12):2372–2376. doi: 10.1021/bi00788a030. [DOI] [PubMed] [Google Scholar]

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