STIMULATION OF CALCIUM INFLUX AND PLATELET ACTIVATION BY CANATOXIN - METHOXYVERAPAMIL INHIBITION AND DOWN-REGULATION BY CGMP

Canatoxin (CNTX), a toxic protein isolated from seeds of Canavalia ens iformis, induces Ca2+ influx across the platelet plasma membrane, mobi lization of arachidonic acid mediated by phospholipase A,, ATP secreti on, and platelet aggregation. All these events depend on the presence of extracellular Ca2+ and are blocked by methoxyverapamil, a calcium-c hannel blocker. CNTX does not activate phospholipase C, and the intrac ellular calcium mobilization mediated by IP3 does not play a role in p latelet activation by this toxin. Preincubation of rabbit platelets wi th 8-Br-cGMP inhibited the CNTX-evoked calcium influx, arachidonate re lease, ATP secretion, and cell aggregation. Our data suggest that the calcium influx is a prior step on platelet activation by CNTX, being m odulated by cGMP. (C) 1997 Academic Press.