Inhibition of Platelet Activation by Marine Sterols from Octocorals

팔방산호충류에서 분리한 해양 스테롤 화합물의 혈소판 응집 억제작용

  • Published : 1997.10.01

Abstract

The purpose of this investigation was to determine the inhibition on $Na^+,\;K^+$-ATPase, cyclic AMP phosphodiesterase and platelet activation by marine sterols isolated from octocorals. Three marine polyhydroxysterols, 7${\alpha},\;8{\alpha}-epoxy-3b{\beta},\;5{\alpha},\;6{\alpha}-trihydroxycholestane (1),\;24-methyl-7{\alpha},\;8{\alpha}-epoxy-3{\beta},\;5{\alpha},\;6{\alpha}-trihydroxycholest-22-ene (2),\;and\;7{\alpha},\;8{\alpha}-epoxy-3{\beta},\;5{\alpha},\;6{\alpha}-trihydroxycholest-22-ene (3)$, were isolated from the Gorgonian Acabaria undulata. Five marine sterols(compound 4, 5, 6, 7, 8) were isolated from the soft coral Alcyonium gracillimum. Three marine polyhydroxysterols (1, 2, 3) and pregna-1. 20-diene-3-one (8) exhibit a potent inhibitory effect on rabbit platelet aggregation induced by collagen and thrombin. Those polyhydroxysterols also exhibit a potent inhibitory effect on cyclic AMP phosphodiesterase. Compound 6 with an unusual cyclic enolether exhibit a inhibitory effect on $Na^+,\;K^+$-ATPase.

Keywords

References

  1. v.1 Bioorganic marine chemistry. Ed. Scheuer. P. J.
  2. 海洋生物のchemical signal 北川勳;伏谷伸광
  3. 化學增刊 v.121 化學て探る海洋生物の謎. 安元健
  4. Chem. Rev. v.93 Bioactive methabolites of symbiotic marine microdrganism. Kobayashi, J.;Ishibashi, M.
  5. Chem. Rev. v.93 Marine toxins. Yasumoto, T.;Murata, M.
  6. Cellular Signalling v.9 Total inhibition of phospholipase C and phosphatidylinositol 3-kinase by okadaic acid in thrombinstimulated platelets. Mauco, G.;Artcanuthurry, V.;Pidard, D.;Grelac, F.;Maclouf, J.;Levytoledano, S.
  7. J. Fd. Hyg. Safety v.10 Effect of marine toxins on the rabbit platelets. Park, Y. H.
  8. J. Am. Chem. Soc. v.114 Partial structures of maitotoxin from dinoflagellate Gambierdiscus toxicus. Murata, M.;Iwashita, T.;Yokoyama, A.;Sasaki, M.;Yasumoto, T.
  9. J. Biol. Chem. v.268 High affinity binding of 9-$[^1H]$ methyl-7-bromoeu distomin D to the caffeine-binding site of skeletal muscle sarcoplasmic reticulum. Fang, Y. I.;Adachi, M.;Kobayashi, J.;Ohizumi, Y.
  10. J. Pharm. Pharmacol. v.46 Properties of the binding sites of $[^3H]$ 9-methyl-7-bromoeudistomin D in bovine aortic smooth muscle microsomes. Adachi, M.;Fang, Y. I.;Kobayashi, J.;Yamakuni, T.;Ohizumi, Y.
  11. J. Pharm. Pharmacol. v.46 Tissue-and subcellular-distribution of the binding site of $[^3H]$ 9-methyl-7-bromoeudistomin D, a potent caffeine-like $Ca^{2+}$ releaser. Adachi, M.;Kakubari, M.;Ohizumi, Y.
  12. Natural Product Reports v.465 Marine sterols. Kerr. R. G.;Baker, B. J.
  13. Cell Calcium v.17 Distribution of plasma membrance $Ca^{2+}$-ATPase and inositon 1, 4, 5-trisphosphate receptor in human platelet membranes. Dean, W. L.;Quinton T. M.
  14. Eur. J. Biochem. v.239 Calcium influx is a determining factors of calpain activation and microparticle formation in platelets. Pasquet, J. M.;Dacharyprigent, J;Nurden, A. T.
  15. Acabaria undulata. J. Nat. Prod. v.59 Isolation of polyhydroxysteroids from the gorgonian Shin, J.;Seo, Y.;Rho, J. -R.;Cho, K. W.
  16. Alcyonium gracillimum. Tetrahedron v.51 Isolation of novel bioactive steroids from the soft coral Seo, Y.;Jung, J. H.;Rho, J. -R.;Shin, J.;Song, J. -R.
  17. Nature v.194 Aggregation of blood platelets by adenosine diphosphate and its reversal. Born, G. V. R.
  18. Phytochemistry v.40 Steroidal saponins from Allium chinensis and their inhibitory activities on cyclic AMP phosphodiesterase and $Na^+, K^+$-ATPase. Kuroda, M.;Mimaki, Y.;Sashida, Y.;Nikaido, T.
  19. 海洋生物のchemical signal 北川勳;伏谷伸광
  20. v.10 Marine resources for drug discovery I, The 2nd series of pharmaceutical reseach and devolopment. Yajima, H.;Shioiri, T.;Ohizumi, Y.
  21. Phytochemistry v.20 Sterols with unusual nuclear unsaturation from three cultured marine dinoflagellates. Kokke, W. C. M.;Fenical, W.;Djerassi, C.
  22. Ophiarachna incrassata. J. Nat. Prod. v.57 In hibitors of protein tyrosine kinase pp60 : Sterol sulfates from the brittle star Lee, R. H.;Papkoff, J. S.;Slate, D. L.
  23. Marine Natural Products. Vol. 2, Ed. Scheuer, P. J. Goad, L. J.
  24. Br. J. Pharmacol. v.109 $Ca^{2+}$-dependent aggregation of rabbit platelets induced by maitotoxin, a potent marine toxin, isolated from a dinoflagellate. Watanabe, A.;Ishida, Y.;Honda, H.;Kobayashi, M.;Ohizumi, Y.
  25. Theonella sp., Can J. Physiol. Pharmacol. v.74 The mode of rabbit platelet shape change and aggregation induced by theonezolide-A, anovel polyketide macrolide, isolated from the Okinawan marine sponge Rho, M. C.;Park, Y. H.;Sasaki, S.;Ishibashi, M.;Kondo, K.;Kobayashi, J.;Ohizumi, Y.
  26. J. Pharmacol. Meth. v.9 Turbidometric evaluations of platelet aggregation : relative contributions of measured shape change, volume, and early aggregation. Milton, J. G.;Frojmovic, M. M.
  27. Annu. Rev. Physiol. v.52 Calcium signaling in human platelets. Rink, T. J.;Sage, S. O.
  28. Folia Pharmacol. Jpn. v.106 Selective type Ⅲ phosphodiesterase inhibitor as an antithrombotic agent. Kimura, Y.
  29. The Pharmacological Basis of Therapeutics. 9th. Giman G. A.;gilman, L. S.