15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and maitotoxin

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+.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Blood Platelets; Blotting, Western; Calcium; Hydrolysis; Male; Marine Toxins; Microscopy, Electron, Scanning; Oxocins; Phosphatidylinositols; Phosphorylation; Platelet Activation; Platelet Aggregation; Rabbits; Thromboxane A2; Tyrosine