Comparison of maitotoxin with thromboxane A2 in rabbit platelet activation.
Maitotoxin (MTX), a Ca2+ channel-activating marine toxin, caused shape change followed by aggregation in rabbit platelets, like U46619, a thromboxane A2 analogue. Although both drugs failed to cause aggregation in the absence of external Ca2+, U46619, but not maitotoxin, elicited shape change in the absence of external Ca2+. The observations of platelets with a scanning electron microscope showed that both drugs caused contraction of platelets and extension of pseudopodia (shape change) followed by aggregation with a clot in the presence of Ca2+. It is noteworthy that long term exposure to MTX caused the lysis of platelets in the presence of Ca2+. While U46619 transiently increased the internal Ca2+ concentration ([Ca2+]i), maitotoxin slowly but irreversibly increased [Ca2+]i in an external Ca2(+)-dependent manner. MTX-induced phosphoinositide hydrolysis was totally dependent on the presence of external Ca2+, but U46619-induced phosphoinositide hydrolysis was still observed in the absence of external Ca2+. MTX-induced phosphoinositide hydrolysis was partly inhibited by SK&F96365, a voltage-independent Ca2+ channel antagonist, or by genistein, a tyrosine kinase inhibitor. MTX caused phosphorylation of tyrosine residues of several proteins, like U46619. Thus, MTX is similar to U46619 in functions of Ca2+ mobilization, phosphoinositide hydrolysis and tyrosine phosphorylation, but MTX-induced actions are strictly dependent on the presence of external Ca2+.
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. nakahata@mail.pharm.tohoku.ac.jp
N
N
Nakahata
S
S
Ohkubo
E
E
Ito
M
M
Nakano
K
K
Terao
Y
Y
Ohizumi
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015153:Blotting, Western; D002118:Calcium / Q000097:blood; D006868:Hydrolysis; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D035964:Oxocins; D010716:Phosphatidylinositols / Q000097:blood; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013928:Thromboxane A2 / Q000819:agonists / Q000494:pharmacology*; D014443:Tyrosine / Q000097:blood; D000095702:Polyether Toxins
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium; D008387:Marine Toxins; D035964:Oxocins; D010716:Phosphatidylinositols; D013928:Thromboxane A2; D014443:Tyrosine; C020394:maitotoxin; D000095702:Polyether Toxins