CA-2+-DEPENDENT AGGREGATION OF RABBIT PLATELETS INDUCED BY MAITOTOXIN, A POTENT MARINE TOXIN, ISOLATED FROM A DINOFLAGELLATE

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. The MTX-induced platelet aggregation and [Ca2+]i-increase were totally abolished in a Ca2+-free solution. The successive administration of Ca2+ in the presence of MTX elicited the aggregation and increase in [Ca2+]i. 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. 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. MTX also elicited a release of ATP from platelets, which was abolished in the absence of external Ca2+. 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+. These results suggest that the MTX-induced platelet activation is caused by an enhanced Ca2+-influx presumably through voltage-independent Ca2+ channels on the plasma membrane.