Comparison of maitotoxin with thromboxane A2 in rabbit platelet activation

• Published in: Toxicon (Oxford) 1999-10, Vol.37 (10), p.1375-1389
• Main Authors: NAKAHATA, N, OHKUBO, S, ITO, E, NAKANO, M, TERAO, K, OHIZUMI, Y
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Animals; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood Platelets - ultrastructure; Blotting, Western; Calcium - blood; Hydrolysis; Male; Marine Toxins - pharmacology; Medical sciences; Microscopy, Electron, Scanning; Oxocins; Phosphatidylinositols - blood; Phosphorylation; Plant poisons toxicology; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Rabbits; Thromboxane A2 - agonists; Thromboxane A2 - pharmacology; Toxicology; Tyrosine - blood
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/S0041-0101(99)00081-1

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+.