Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 May;109(1):29–36. doi: 10.1111/j.1476-5381.1993.tb13527.x

Ca(2+)-dependent aggregation of rabbit platelets induced by maitotoxin, a potent marine toxin, isolated from a dinoflagellate.

A Watanabe 1, Y Ishida 1, H Honda 1, M Kobayashi 1, Y Ohizumi 1
PMCID: PMC2175570  PMID: 8495244

Abstract

1. Administration of maitotoxin (MTX), a dinoflagellate toxin, caused aggregation of rabbit washed platelets. The cytosolic Ca2+ concentration ([Ca2+]i), measured by fura-2 fluorescence technique, was also increased by the presence of MTX. Rates of aggregation response and [Ca2+]i-increase were dependent on tested concentrations (3-100 ng ml-1) of the toxin. 2. The MTX-induced platelet aggregation and [Ca2+]i-increase were totally abolished in a Ca(2+)-free solution. The successive administration of Ca2+ in the presence of MTX elicited the aggregation and increase in [Ca2+]i. 3. Ba2+ was capable of substituting for Ca2+ in the MTX-induced platelet aggregation. In the presence of external Ca2+, transition metals, Co2+, Cd2+ and Ni2+, inhibited the aggregation response to MTX. 4. Organic calcium antagonists (verapamil and nifedipine) as well as a cyclo-oxygenase-inhibitor (aspirin) did not apparently inhibit the aggregation response to MTX, except for a high concentration (10(-5) M) of verapamil, while procaine (10 mM) reduced the rate of platelet aggregation. 5. MTX also elicited a release of ATP from platelets, which was abolished in the absence of external Ca2+. 6. In contrast, thrombin 0.5 unit ml-1 could elicit platelet shape change, [Ca2+]i-increase and ATP-release in the absence of external Ca2+. 7. These results suggest that the MTX-induced platelet activation is caused by an enhanced Ca(2+)-influx presumably through voltage-independent Ca2+ channels on the plasma membrane.

Full text

PDF
32

Selected References

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

  1. Avdonin P. V., Men'shikov MYu, Svitina-Ulitina I. V., Tkachuk V. A. Blocking of the receptor-stimulated calcium entry into human platelets by verapamil and nicardipine. Thromb Res. 1988 Dec 15;52(6):587–597. doi: 10.1016/0049-3848(88)90131-4. [DOI] [PubMed] [Google Scholar]
  2. Berta P., Phaneuf S., Derancourt J., Casanova J., Durand-Clement M., le Peuch C., Haiech J., Cavadore J. C. The effects of maitotoxin on phosphoinositides and calcium metabolism in a primary culture of aortic smooth muscle cells. Toxicon. 1988;26(2):133–141. doi: 10.1016/0041-0101(88)90165-1. [DOI] [PubMed] [Google Scholar]
  3. Doyle V. M., Rüegg U. T. Lack of evidence for voltage dependent calcium channels on platelets. Biochem Biophys Res Commun. 1985 Feb 28;127(1):161–167. doi: 10.1016/s0006-291x(85)80139-x. [DOI] [PubMed] [Google Scholar]
  4. Faivre J. F., Deroubaix E., Coulombe A., Legrand A. M., Coraboeuf E. Effect of maitotoxin on calcium current and background inward current in isolated ventricular rat myocytes. Toxicon. 1990;28(8):925–937. doi: 10.1016/0041-0101(90)90022-y. [DOI] [PubMed] [Google Scholar]
  5. Freedman S. B., Miller R. J., Miller D. M., Tindall D. R. Interactions of maitotoxin with voltage-sensitive calcium channels in cultured neuronal cells. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4582–4585. doi: 10.1073/pnas.81.14.4582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Godfraind T., Miller R., Wibo M. Calcium antagonism and calcium entry blockade. Pharmacol Rev. 1986 Dec;38(4):321–416. [PubMed] [Google Scholar]
  7. Gusovsky F., Daly J. W. Maitotoxin: a unique pharmacological tool for research on calcium-dependent mechanisms. Biochem Pharmacol. 1990 Jun 1;39(11):1633–1639. doi: 10.1016/0006-2952(90)90105-t. [DOI] [PubMed] [Google Scholar]
  8. Gusovsky F., Yasumoto T., Daly J. W. Maitotoxin, a potent, general activator of phosphoinositide breakdown. FEBS Lett. 1989 Jan 30;243(2):307–312. doi: 10.1016/0014-5793(89)80151-6. [DOI] [PubMed] [Google Scholar]
  9. Hallam T. J., Rink T. J. Agonists stimulate divalent cation channels in the plasma membrane of human platelets. FEBS Lett. 1985 Jul 8;186(2):175–179. doi: 10.1016/0014-5793(85)80703-1. [DOI] [PubMed] [Google Scholar]
  10. Hamberg M., Svensson J., Samuelsson B. Letter: Mechanism of the anti-aggregating effect of aspirin on human platelets. Lancet. 1974 Jul 27;2(7874):223–224. doi: 10.1016/s0140-6736(74)91525-6. [DOI] [PubMed] [Google Scholar]
  11. Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jy W., Haynes D. H. Thrombin-induced calcium movements in platelet activation. Biochim Biophys Acta. 1987 Jun 15;929(1):88–102. doi: 10.1016/0167-4889(87)90244-8. [DOI] [PubMed] [Google Scholar]
  13. Kobayashi M., Kondo S., Yasumoto T., Ohizumi Y. Cardiotoxic effects of maitotoxin, a principal toxin of seafood poisoning, on guinea pig and rat cardiac muscle. J Pharmacol Exp Ther. 1986 Sep;238(3):1077–1083. [PubMed] [Google Scholar]
  14. Kobayashi M., Miyakoda G., Nakamura T., Ohizumi Y. Ca-dependent arrhythmogenic effects of maitotoxin, the most potent marine toxin known, on isolated rat cardiac muscle cells. Eur J Pharmacol. 1985 Apr 23;111(1):121–123. doi: 10.1016/0014-2999(85)90120-7. [DOI] [PubMed] [Google Scholar]
  15. Kobayashi M., Ochi R., Ohizumi Y. Maitotoxin-activated single calcium channels in guinea-pig cardiac cells. Br J Pharmacol. 1987 Nov;92(3):665–671. doi: 10.1111/j.1476-5381.1987.tb11370.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kobayashi M., Ohizumi Y., Yasumoto T. The mechanism of action of maitotoxin in relation to Ca2+ movements in guinea-pig and rat cardiac muscles. Br J Pharmacol. 1985 Oct;86(2):385–391. doi: 10.1111/j.1476-5381.1985.tb08907.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Legrand A. M., Bagnis R. Effects of highly purified maitotoxin extracted from dinoflagellate Gambierdiscus toxicus on action potential of isolated rat heart. J Mol Cell Cardiol. 1984 Jul;16(7):663–666. doi: 10.1016/s0022-2828(84)80630-6. [DOI] [PubMed] [Google Scholar]
  18. Login I. S., Judd A. M., MacLeod R. M. Activation of calcium channels by maitotoxin. Methods Enzymol. 1987;141:63–79. doi: 10.1016/0076-6879(87)41056-2. [DOI] [PubMed] [Google Scholar]
  19. Milton J. G., Frojmovic M. M. Turbidometric evaluations of platelet activation: relative contributions of measured shape change, volume, and early aggregation. J Pharmacol Methods. 1983 Apr;9(2):101–115. doi: 10.1016/0160-5402(83)90002-5. [DOI] [PubMed] [Google Scholar]
  20. Miyamoto T., Ohizumi Y., Washio H., Yasumoto Y. Potent excitatory effect of maitotoxin on Ca channels in the insect skeletal muscle. Pflugers Arch. 1984 Apr;400(4):439–441. doi: 10.1007/BF00587546. [DOI] [PubMed] [Google Scholar]
  21. Ohizumi Y., Kajiwara A., Yasumoto T. Excitatory effect of the most potent marine toxin, maitotoxin, on the guinea-pig vas deferens. J Pharmacol Exp Ther. 1983 Oct;227(1):199–204. [PubMed] [Google Scholar]
  22. Ohizumi Y., Yasumoto T. Contractile response of the rabbit aorta to maitotoxin, the most potent marine toxin. J Physiol. 1983 Apr;337:711–721. doi: 10.1113/jphysiol.1983.sp014650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ohizumi Y., Yasumoto T. Contraction and increase in tissue calcium content induced by maitotoxin, the most potent known marine toxin, in intestinal smooth muscle. Br J Pharmacol. 1983 May;79(1):3–5. doi: 10.1111/j.1476-5381.1983.tb10485.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pollock W. K., Rink T. J., Irvine R. F. Liberation of [3H]arachidonic acid and changes in cytosolic free calcium in fura-2-loaded human platelets stimulated by ionomycin and collagen. Biochem J. 1986 May 1;235(3):869–877. doi: 10.1042/bj2350869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pollock W. K., Rink T. J. Thrombin and ionomycin can raise platelet cytosolic Ca2+ to micromolar levels by discharge of internal Ca2+ stores: studies using fura-2. Biochem Biophys Res Commun. 1986 Aug 29;139(1):308–314. doi: 10.1016/s0006-291x(86)80114-0. [DOI] [PubMed] [Google Scholar]
  26. Rink T. J., Sage S. O. Calcium signaling in human platelets. Annu Rev Physiol. 1990;52:431–449. doi: 10.1146/annurev.ph.52.030190.002243. [DOI] [PubMed] [Google Scholar]
  27. Rink T. J., Smith S. W., Tsien R. Y. Cytoplasmic free Ca2+ in human platelets: Ca2+ thresholds and Ca-independent activation for shape-change and secretion. FEBS Lett. 1982 Nov 1;148(1):21–26. doi: 10.1016/0014-5793(82)81234-9. [DOI] [PubMed] [Google Scholar]
  28. Sage S. O., Rink T. J. The kinetics of changes in intracellular calcium concentration in fura-2-loaded human platelets. J Biol Chem. 1987 Dec 5;262(34):16364–16369. [PubMed] [Google Scholar]
  29. Siess W. Molecular mechanisms of platelet activation. Physiol Rev. 1989 Jan;69(1):58–178. doi: 10.1152/physrev.1989.69.1.58. [DOI] [PubMed] [Google Scholar]
  30. Sladeczek F., Schmidt B. H., Alonso R., Vian L., Tep A., Yasumoto T., Cory R. N., Bockaert J. New insights into maitotoxin action. Eur J Biochem. 1988 Jul 1;174(4):663–670. doi: 10.1111/j.1432-1033.1988.tb14149.x. [DOI] [PubMed] [Google Scholar]
  31. Smith J. B., Willis A. L. Aspirin selectively inhibits prostaglandin production in human platelets. Nat New Biol. 1971 Jun 23;231(25):235–237. doi: 10.1038/newbio231235a0. [DOI] [PubMed] [Google Scholar]
  32. Takahashi M., Ohizumi Y., Yasumoto T. Maitotoxin, a Ca2+ channel activator candidate. J Biol Chem. 1982 Jul 10;257(13):7287–7289. [PubMed] [Google Scholar]
  33. Takahashi M., Tatsumi M., Ohizumi Y., Yasumoto T. Ca2+ channel activating function of maitotoxin, the most potent marine toxin known, in clonal rat pheochromocytoma cells. J Biol Chem. 1983 Sep 25;258(18):10944–10949. [PubMed] [Google Scholar]
  34. Thompson N. T., Scrutton M. C. Intracellular calcium fluxes in human platelets. Eur J Biochem. 1985 Mar 1;147(2):421–427. doi: 10.1111/j.1432-1033.1985.tb08766.x. [DOI] [PubMed] [Google Scholar]
  35. Ueda H., Tamura S., Fukushima N., Takagi H. Pertussis toxin (IAP) enhances maitotoxin (a putative Ca2+ channel agonist)-induced Ca2+ entry into synaptosomes. Eur J Pharmacol. 1986 Apr 2;122(3):379–380. doi: 10.1016/0014-2999(86)90421-8. [DOI] [PubMed] [Google Scholar]
  36. Ueda H., Tamura S., Harada H., Yasumoto T., Takagi H. The maitotoxin-evoked Ca2+ entry into synaptosomes is enhanced by cholera toxin. Neurosci Lett. 1986 Jun 18;67(2):141–146. doi: 10.1016/0304-3940(86)90387-3. [DOI] [PubMed] [Google Scholar]
  37. Yokoyama A., Murata M., Oshima Y., Iwashita T., Yasumoto T. Some chemical properties of maitotoxin, a putative calcium channel agonist isolated from a marine dinoflagellate. J Biochem. 1988 Aug;104(2):184–187. doi: 10.1093/oxfordjournals.jbchem.a122438. [DOI] [PubMed] [Google Scholar]
  38. Yoshii M., Tsunoo A., Kuroda Y., Wu C. H., Narahashi T. Maitotoxin-induced membrane current in neuroblastoma cells. Brain Res. 1987 Oct 20;424(1):119–125. doi: 10.1016/0006-8993(87)91200-5. [DOI] [PubMed] [Google Scholar]
  39. Zschauer A., van Breemen C., Bühler F. R., Nelson M. T. Calcium channels in thrombin-activated human platelet membrane. Nature. 1988 Aug 25;334(6184):703–705. doi: 10.1038/334703a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES