Stimulation of calcium influx and platelet activation by canatoxin: methoxyverapamil inhibition and downregulation by cGMP.
Canatoxin (CNTX), a toxic protein isolated from seeds of Canavalia ensiformis, induces Ca2+ influx across the platelet plasma membrane, mobilization of arachidonic acid mediated by phospholipase A2, ATP secretion, and platelet aggregation. All these events depend on the presence of extracellular Ca2+ and are blocked by methoxyverapamil, a calcium-channel blocker. CNTX does not activate phospholipase C, and the intracellular calcium mobilization mediated by IP3 does not play a role in platelet activation by this toxin. Preincubation of rabbit platelets with 8-Br-cGMP inhibited the CNTX-evoked calcium influx, arachidonate release, ATP secretion, and cell aggregation. Our data suggest that the calcium influx is a prior step on platelet activation by CNTX, being modulated by cGMP.
Ghazaleh
F A
FA
ICB, Federal University of Rio de Janeiro, Cidade Universitária, Rio de Janeiro, Ilha do Fundão, CEP 21941-590, Brazil.
Francischetti
I M
IM
Gombarovits
M E
ME
Carlini
C R
CR
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D015536:Down-Regulation; D004347:Drug Interactions; D005711:Gallopamil / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D037102:Lectins / Q000494:pharmacology*; D010940:Plant Proteins; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014118:Toxins, Biological
D002121:Calcium Channel Blockers; D037102:Lectins; D010940:Plant Proteins; D010975:Platelet Aggregation Inhibitors; D014118:Toxins, Biological; D005711:Gallopamil; C032815:canatoxin; D006152:Cyclic GMP; D002118:Calcium