Inhibition of $Na^+,\;K^+$$-ATPase, cyclicAMP Phonsphodiesterase and Platelet Activation by Secondary Metabolites from Marine Organisms

혈소판 및 $Na^+,\;K^+$$-ATPase, cyclicAMP 포스포디에스테라제에 대한 해양천연물질의 작용

  • Published : 1997.06.01

Abstract

The purpose of this investigation was to determine the inhibition of $Na^+,\;K^+$-ATPase, cyclicAMP phophodiesterase and platelet activation by secondary metabolites isolated from mar ine organisms. The secondary metabolites were isolated and identified as six diterpenoids(1 : astrogorgin, 2 : ophirin, 3 : calicophirin B, 4, 5 and 6 : cladiellin) from the dichloromethane extract of Muricellajsp., four ceramides(1,2,3, and 4) from Acabaria undulata and three antharaquinones(1,2 : crysophanol, and 3 : physcion) from Urechis unicintus. The results demonstrated that diterpenoids(2,3, and 4) showed the inhibition of cyclicAMP phosphodiesterase, and ceramides(1,3, and 4) showed the inhibition of cyclicAMP phosphodiesterase and thrombin(0.1 units/ml)-induced aggregation of washed rabbit platelet, and anthrapuinones((1,2, and 3) showed the inhibition of $Na^+,\;K^+$-ATPase. Among the anthraquionones, 1,2-dimethoxy-3-methyl-8-hydroxy-anthraquinone(1) showed the inhibition of collagen(1.0 ${\mu}g$/ml)-induced aggregation in a concenration-dependent manner with IC50 value of 42.8 ${\mu}g$M.

Keywords

References

  1. Bioorganic marine chemistry v.1-6 Scheuer, P. J.(ed.)
  2. Marine Natural Products Chemical and biological perspectives Shimizu, H.;Scheuer, P. J.(ed.)
  3. 化學增刊 v.111 海洋天然物化學 北川勳
  4. Chem. Rev. v.93 Bioactive methabolites of symbiotic marine microdrganism Kobayashi J.;Ishibashi M.
  5. BIOmedica v.7 海洋天然物質の醫療應用 北川勳
  6. 化學增刊 v.121 化學で探る海洋生物の謎 安元健
  7. Chem. Rev. v.93 Microalgal methabolites Shimizu. Y.
  8. Chem. Rev. v.93 Marine toxins Yasumoto, T.;Murata, M.
  9. Toxic Dinoflagellate Blooms. Ed. A new toxic dinoflagellate found in association with ciguatera Yasumoto, T.;Nakajima, I.;Oshima, Y.;Bagnis, R.;Taylor, D. L. (ed.);Seliger, H.(ed.)
  10. J. Am. Chem. Soc. v.114 Partial structures of maitotoxin from dinoflagellate Gambierdiscus toxicus Murata, M.;Iwashita, T.;Yokoyama, A.;Sasaki, M.;Yasumoto, T.
  11. J. Fd. Hyg. Safety v.10 Effect of marine toxins on the rabbits Park, Y. H.
  12. J. Biol. Chem. v.268 High affinity binding of 9-[¹H] methyl-7-bromoeu distomin D to the caffeinebinding site of skeletal muscle sarcoplasmic reticulum Fang, Y. I.;Adachi, M.;Kobayashi, J.;Ohizumi, Y.
  13. J. Pharm. Pharmacol. v.46 Properties of the binding sites of [³H]9-methyl-7-bromoeu-distomin D in bovine aortic smooth muscle microsomes Adachi, M.;Fang, Y. I.;Kobayashi, J.;Yamakuni, T.;Ohizumi, Y.
  14. 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.
  15. Biol. Chem. HoppeSeyler v.375 The specific binding site of 9[³H]-methyl-7-biomoeudistomin D, a caffeine-like $Ca^{2+}$ releaser in liver microsomes is distnet from that in skeletal sarcoplasmic reticulum. Adachi, M.;Kakubari, M.;Ohizumi, Y.
  16. Theonella sp., Can J. Physiol. Pharmacol. v.74 The mode of rabbit platelet shape change and aggregation induced by theonezolide-A. a novel polyketide macrolide. isolated from the Okinawan marine sponge Rho, M. C.;Park, Y. H.;Sasaki, S.;Ishibashi, M.;Kondo, K.;Kobayashi, J.;Ohizumi, Y.
  17. 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.
  18. Phytochemistry v.40 Steroidal saponins from Allium chinensis and their inhibitory activites on cyclic AMP phosphodiesterase and $Na^+$, K-ATPase Kuroda, M.;Mimaki, Y.;Sashida, Y.;Nikaido, T.
  19. Nature v.194 Aggregation of blood platelets by adenosine diphosphate and its reversal Born, G. V. R.
  20. 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.
  21. Marine resources for drug discovery I. The 2nd series of pharmaceutical research and development v.10 Yajima, H.(ed.);Shioiri, T.(ed.);Ohizumi, Y.(ed.)
  22. J. Nat. Prod. v.58 Isolation of new ceramides from the gorgonian Acabaria undulata Shin, J. H.;Seo, Y. W.
  23. J. Nat. Prod. Isolation of anthraquinones from the Echiuran urechia unicintus Park, Y. H.;Chang, S. K.;Kim, I. K.
  24. Planta Medica v.50 Isolation and characterization of the major anthraquinone pigments from Rumex abysinica Munavu, R. M.;Mudamba, L. O.;Ogur, J. A.
  25. 海洋生物のchemical signal 北川勳;伏谷伸宏
  26. Annu. Rev. Physiol. v.52 Calcium signaling in human platelets Rink, T. J.;Sage, S. O.