Convulxin-induced activation of intact and of thrombin-degranulated rabbit platelets: specific crossed desensitisation with collagen.
The aggregation of plasma-free rabbit platelets induced by convulxin (Cx), a glycoprotein extracted from the venom of Crotalus durissus cascavella was accompanied by the secretion of ATP and by the formation of thromboxane A2 (TxA2) and of 'platelet-activating factor' (PAF-acether). Thrombin-induced exhaustion of the pool of releasable ADP, or inactivation of cyclooxygenase with aspirin or with arachidonic acid failed to suppress Cx-induced activation. Electron microscopy studies showed that platelets exposed to Cx could be recovered without damage to the cytoplasmic membrane, whereas dense bodies were depleted. Convulxin-treated platelets aggregated in response to ADP, to arachidonic acid and to thrombin, but failed to aggregate in response to Cx itself as well as to collagen. Crossed desensitisation between Cx and collagen was also observed when platelets were exposed to Cx in the presence of prostaglandin E1, which prevented granule depletion, demonstrating that desensitisation was not due to the inability of Cx-treated platelets to secrete ADP in response to collagen. Formation of PAF-acether by thrombin-treated platelets was impaired when thrombin was used as a second stimulus but was maintained when Cx was used as such. The formation of TxA2 by Cx-treated platelets stimulated with arachidonic acid or with thrombin was preserved of only slightly reduced whereas these platelets failed to synthesize TxA2 when stimulated with Cx or with collagen, showing that crossed desensitization between Cx and collagen was not restricted to aggregation, but extended to stimulation of arachidonate metabolism as well. Convulxin is a powerful platelet-stimulating agent which operates through mechanisms which may involve PAF-acether, and which interacts with sites related with those of collagen at an unknown level.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D003094:Collagen / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000494:pharmacology*; D037181:Lectins, C-Type; D010972:Platelet Activating Factor / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology*
D001095:Arachidonic Acids; D003435:Crotalid Venoms; D037181:Lectins, C-Type; D010972:Platelet Activating Factor; C028890:convulxin; D000255:Adenosine Triphosphate; D003094:Collagen; D013917:Thrombin