Ca(2+)-dependent aggregation of rabbit platelets induced by maitotoxin, a potent marine toxin, isolated from a dinoflagellate.
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.
Department of Pharmaceutical Molecular Biology, Tohoku University, Miyagi, Japan.
A
A
Watanabe
Y
Y
Ishida
H
H
Honda
M
M
Kobayashi
Y
Y
Ohizumi
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D004141:Dinoflagellida / Q000378:metabolism*; D016257:Fura-2; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D035964:Oxocins; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology; D000095702:Polyether Toxins
D000255:Adenosine Triphosphate; D002118:Calcium; D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D016257:Fura-2; D008387:Marine Toxins; D035964:Oxocins; D013917:Thrombin; C020394:maitotoxin; D000095702:Polyether Toxins