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. 1981 Oct;74(2):435–444. doi: 10.1111/j.1476-5381.1981.tb09989.x

Metabolites of arachidonic acid formed by human gastrointestinal tissues and their actions on the muscle layers.

A Bennett, C N Hensby, G J Sanger, I F Stamford
PMCID: PMC2071735  PMID: 7317691

Abstract

1. Gas chromatography-mass spectrometry demonstrated the presence of arachidonic acid (AA), 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) in all extracts of homogenized muscle or mucosa from human stomach, terminal ileum or sigmoid colon. Prostaglandin D2 (PGD2), PGE2 or PGF2 alpha were usually found more often in the mucosal extracts. The 12-hydroxy-derivative of AA (12-HETE) was detected in all extracts of the colon but in only some of the other tissues. 2. Most prostanoids tested contracted the longitudinal muscle, the order of potency being U-46619 (an epoxymethano analogue of PGH2) greater than PGE2 greater than PGF2 alpha greater than PGD2; PGI2 usually caused relaxation, whereas its breakdown products or TxB2 had weak and variable effects. 3. U-46619 or, less potently, PGF2 alpha contracted the circular muscle, whereas PGI2 and usually PGE2 caused relaxation. PGD2, 6-keto-PGF1 alpha, 6,15-diketo-PGF1 alpha or TxB2 usually had little or no effect. 4. PGI2 antagonized contractions to some excitatory prostanoids, without greatly affecting contractions to acetylcholine. 5. For both muscle layers there was a gradient in sensitivity to prostanoids along the gastrointestinal tract. The sensitivities were stomach greater than distal ileum greater than sigmoid colon. 6. The results are discussed in relation to gastrointestinal physiology and pathophysiology.

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Selected References

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  1. Adaikan P. G., Karim S. M. Effects of PGA and PGB compounds on gastrointestinal tract smooth muscle from man and laboratory animals. Prostaglandins. 1976 Jan;11(1):15–22. doi: 10.1016/0090-6980(76)90168-4. [DOI] [PubMed] [Google Scholar]
  2. Ali M., Zamecnik J., Cerskus A. L., Stoessl A. J., Barnett W. H., McDonald J. W. Synthesis of thromboxane B2 and prostaglandins by bovine gastric mucosal microsomes. Prostaglandins. 1977 Nov;14(5):819–827. doi: 10.1016/0090-6980(77)90299-4. [DOI] [PubMed] [Google Scholar]
  3. Anders N. H. Preparative thin-layer and column chromatography of prostaglandins. J Lipid Res. 1969 May;10(3):316–319. [PubMed] [Google Scholar]
  4. Bennett A., Fleshler B. Prostaglandins and the gastrointestinal tract. Gastroenterology. 1970 Nov;59(5):790–800. [PubMed] [Google Scholar]
  5. Bennett A., Jarosik C., Sanger G. J., Wilson D. E. Antagonism of prostanoid-induced contractions of rat gastric fundus muscle by SC-19220, sodium meclofenamate, indomethacin or trimethoquinol. Br J Pharmacol. 1980;71(1):169–175. doi: 10.1111/j.1476-5381.1980.tb10922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bennett A., Murray J. G., Wyllie J. H. Occurrence of prostaglandin E2 in the human stomach, and a study of its effects on human isolated gastric muscle. Br J Pharmacol Chemother. 1968 Feb;32(2):339–349. [PubMed] [Google Scholar]
  7. Bennett A., Posner J. Studies on prostaglandin antagonists. Br J Pharmacol. 1971 Aug;42(4):584–594. doi: 10.1111/j.1476-5381.1971.tb07142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bennett A., Pratt D., Sanger G. J. Antagonism by fenamates of prostaglandin action in guinea-pig and human alimentary muscle. Br J Pharmacol. 1980 Mar;68(3):357–362. doi: 10.1111/j.1476-5381.1980.tb14548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bennett A., Sanger G. J. Prostacyclin and prostaglandin E2 selectively antagonize responses of human isolated myometrium to excitatory prostaglandins [proceedings]. J Physiol. 1979 Jul;292:36P–37P. [PubMed] [Google Scholar]
  10. Bennett A., Sanger G. J. Prostacyclin relaxes the longitudinal muscle of human isolated stomach and antagonizes contractions to some prostanoids [proceedings]. J Physiol. 1980 Jan;298:45P–46P. [PubMed] [Google Scholar]
  11. Bennett A., Stamford I. F., Stockley H. L. Estimation and characterization of prostaglandins in the human gastrointestinal tract. Br J Pharmacol. 1977 Dec;61(4):579–586. doi: 10.1111/j.1476-5381.1977.tb07551.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bennett A., Stamford I. F., Unger W. G. Prostaglandin E2 and gastric acid secretion in man. J Physiol. 1973 Mar;229(2):349–360. doi: 10.1113/jphysiol.1973.sp010142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Bennett A., Stockley H. L. The contribution of prostaglandins in the muscle of human isolated small intestine to neurogenic responses. Br J Pharmacol. 1977 Dec;61(4):573–578. doi: 10.1111/j.1476-5381.1977.tb07550.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Bennett A., Stockley H. L. The intrinsic innervation of the human alimentary tract and its relation to function. Gut. 1975 Jun;16(6):443–453. doi: 10.1136/gut.16.6.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Bunting S., Moncada S., Vane J. R. The effects of prostagladin endoperoxides and thromboxane A2 on strips of rabbit coeliac artery and certain other smooth muscle preparations [proceedings]. Br J Pharmacol. 1976 Jul;57(3):462P–463P. [PMC free article] [PubMed] [Google Scholar]
  16. Burleigh D. E. The effects of indomethacin on the tone and spontaneous activity of the human small intestine in vitro. Arch Int Pharmacodyn Ther. 1977 Feb;225(2):240–245. [PubMed] [Google Scholar]
  17. Chijimatsu Y., Nguyen T. V., Said S. I. Effects of prostaglandin endoperoxide analogs on contractile elements in lung and gastrointestinal tract. Prostaglandins. 1977 May;13(5):909–916. doi: 10.1016/0090-6980(77)90220-9. [DOI] [PubMed] [Google Scholar]
  18. Coleman R. A., Humphrey P. P., Kennedy I., Levy G. P., Lumley P. U-46619, a selective thromboxane A2-like agonist? [proceedings]. Br J Pharmacol. 1980 Jan;68(1):127P–128P. [PMC free article] [PubMed] [Google Scholar]
  19. Cummings J. H., Newman A., Misiewicz J. J., Milton-Thompson G. J., Billings J. A. Effect of intravenous prostaglandin F 2 on small intestinal function in man. Nature. 1973 May 18;243(5403):169–171. doi: 10.1038/243169a0. [DOI] [PubMed] [Google Scholar]
  20. Gilmore N., Vane J. R., Wyllie J. H. Prostaglandins released by the spleen. Nature. 1968 Jun 22;218(5147):1135–1140. doi: 10.1038/2181135a0. [DOI] [PubMed] [Google Scholar]
  21. Graff G., Stephenson J. H., Glass D. B., Haddox M. K., Goldberg N. D. Activation of soluble splenic cell guanylate cyclase by prostaglandin endoperoxides and fatty acid hydroperoxides. J Biol Chem. 1978 Nov 10;253(21):7662–7676. [PubMed] [Google Scholar]
  22. Ham E. A., Egan R. W., Soderman D. D., Gale P. H., Kuehl F. A., Jr Peroxidase-dependent deactivation of prostacyclin synthetase. J Biol Chem. 1979 Apr 10;254(7):2191–2194. [PubMed] [Google Scholar]
  23. Hamberg M., Hedqvist P., Strandberg K., Svensson J., Samuelsson B. Prostaglandin endoperoxides IV. Effects on smooth muscle. Life Sci. 1975 Feb 1;16(3):451–462. doi: 10.1016/0024-3205(75)90266-0. [DOI] [PubMed] [Google Scholar]
  24. Hammarström S., Falardeau P. Resolution of prostaglandin endoperoxide synthase and thromboxane synthase of human platelets. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3691–3695. doi: 10.1073/pnas.74.9.3691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hong E. Differential pattern of activity of some prostaglandins in diverse superfused tissues. Prostaglandins. 1974 Nov 10;8(3):213–220. doi: 10.1016/0090-6980(74)90044-6. [DOI] [PubMed] [Google Scholar]
  26. Horton E. W., Jones R. L. Prostaglandins A1,A2 and 19-hydroxy A1; their actions on smooth muscle and their inactivation on passage through the pulmonary and hepatic portal vascular beds. Br J Pharmacol. 1969 Nov;37(3):705–722. doi: 10.1111/j.1476-5381.1969.tb08509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hughes J. P., Kadowitz P. J., Hyman A. L., Ray J. E., Joiner P. D. Pharmacology of human isolated colonic circular and longitudinal smooth muscle from cancer and non-cancer patients. Dis Colon Rectum. 1976 Mar;19(2):120–125. doi: 10.1007/BF02590863. [DOI] [PubMed] [Google Scholar]
  28. Hunt R. H., Dilawari J. B., Misiewicz J. J. The effect of intravenous prostaglandin F2 alpha and E2 on the motility of the sigmoid colon. Gut. 1975 Jan;16(1):47–49. doi: 10.1136/gut.16.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Malmsten C. Some biological effects of prostaglandin endoperoxide analogs. Life Sci. 1976 Jan 15;18(2):169–176. doi: 10.1016/0024-3205(76)90021-7. [DOI] [PubMed] [Google Scholar]
  30. Moncada S., Gryglewski R. J., Bunting S., Vane J. R. A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins. 1976 Nov;12(5):715–737. doi: 10.1016/0090-6980(76)90048-4. [DOI] [PubMed] [Google Scholar]
  31. Moncada S., Salmon J. A., Vane J. R., Whittle B. J. Formation of prostacyclin and its product 6-oxo-PGF1alpha by the gastric mucosa of several species [proceedings]. J Physiol. 1978 Feb;275:4P–5P. [PubMed] [Google Scholar]
  32. Oashi S., Omuro S., Toyosaka A., Kuwata K., Miyamoto T. [Proceedings: Effects of prostaglandin E1 on the smooth muscle of human digestive tract]. Nihon Heikatsukin Gakkai Zasshi. 1973 Dec;9(4):237–238. [PubMed] [Google Scholar]
  33. Omini C., Moncada S., Vane J. R. The effects of prostacyclin (PGI2) on tissues which detect prostaglandins (PG'S). Prostaglandins. 1977 Oct;14(4):625–632. doi: 10.1016/0090-6980(77)90189-7. [DOI] [PubMed] [Google Scholar]
  34. Pace-Asciak C. Letter: Isolation, structure, and biosynthesis of 6-ketoprostaglandin F1 alpha in the rat stomach. J Am Chem Soc. 1976 Apr 14;98(8):2348–2349. doi: 10.1021/ja00424a065. [DOI] [PubMed] [Google Scholar]
  35. Pace-Asciak C., Wolfe L. S. A novel prostaglandin derivative formed from arachidonic acid by rat stomach homogenates. Biochemistry. 1971 Sep 28;10(20):3657–3664. doi: 10.1021/bi00796a004. [DOI] [PubMed] [Google Scholar]
  36. Peskar B. M., Seyberth H. W., Peskar B. A. Synthesis and metabolism of endogenous prostaglandins by human gastric mucosa. Adv Prostaglandin Thromboxane Res. 1980;8:1511–1514. [PubMed] [Google Scholar]
  37. Samuelsson B., Borgeat P., Hammarström S., Murphy R. C. Introduction of a nomenclature: leukotrienes. Prostaglandins. 1979 Jun;17(6):785–787. doi: 10.1016/0090-6980(79)90052-2. [DOI] [PubMed] [Google Scholar]
  38. Sanger G. J., Bennett A. Regional differences in the responses to prostanoids of circular muscle from guinea-pig isolated intestine. J Pharm Pharmacol. 1980 Oct;32(10):705–708. doi: 10.1111/j.2042-7158.1980.tb13043.x. [DOI] [PubMed] [Google Scholar]
  39. Siegel M. I., McConnell R. T., Abrahams S. L., Porter N. A., Cuatrecasas P. Regulation of arachidonate metabolism via lipoxygenase and cyclo-oxygenase by 12-HPETE, the product of human platelet lipoxygenase. Biochem Biophys Res Commun. 1979 Aug 28;89(4):1273–1280. doi: 10.1016/0006-291x(79)92146-6. [DOI] [PubMed] [Google Scholar]
  40. Simon B., Kather H. Prostaglandins and the human mucosal alimentary cyclic AMP system. Dig Dis Sci. 1979 Dec;24(12):970–970. doi: 10.1007/BF01311957. [DOI] [PubMed] [Google Scholar]
  41. Simon B., Kather H. Stable prostaglandin endoperoxide analogues and human gastric mucosal adenylate cyclase. Br J Clin Pharmacol. 1980 Jan;9(1):101–102. doi: 10.1111/j.1365-2125.1980.tb04807.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Unger W. G., Stamford I. F., Bennett A. Extraction of prostaglandins from human blood. Nature. 1971 Oct 1;233(5318):336–337. doi: 10.1038/233336b0. [DOI] [PubMed] [Google Scholar]
  43. Whittle B. J., Mugridge K. G., Moncada S. Use of the rabbit transverse stomach-strip to identify and assay prostacyclin, PGA2, PGD2 and other prostaglandins. Eur J Pharmacol. 1979 Jan 1;53(2):167–172. doi: 10.1016/0014-2999(79)90162-6. [DOI] [PubMed] [Google Scholar]

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