Comparison of maitotoxin with thromboxane A 2 in rabbit platelet activation

Abstract

Maitotoxin (MTX), a Ca 2+ channel-activating marine toxin, caused shape change followed by aggregation in rabbit platelets, like U46619, a thromboxane A 2 analogue. Although both drugs failed to cause aggregation in the absence of external Ca 2+, U46619, but not maitotoxin, elicited shape change in the absence of external Ca 2+. 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 Ca 2+. It is noteworthy that long term exposure to MTX caused the lysis of platelets in the presence of Ca 2+. While U46619 transiently increased the internal Ca 2+ concentration ([Ca 2+] i), maitotoxin slowly but irreversibly increased [Ca 2+] i in an external Ca 2+-dependent manner. MTX-induced phosphoinositide hydrolysis was totally dependent on the presence of external Ca 2+, but U46619-induced phosphoinositide hydrolysis was still observed in the absence of external Ca 2+. MTX-induced phosphoinositide hydrolysis was partly inhibited by SK&F96365, a voltage-independent Ca 2+ 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 Ca 2+ mobilization, phosphoinositide hydrolysis and tyrosine phosphorylation, but MTX-induced actions are strictly dependent on the presence of external Ca 2+.