Differential effects of cytochalasin B on platelet release, aggregation and contractility: evidence against a contractile mechanism for the release of platelet granular contents.
Cytochalasin B alters the structure and functional properties of filamentous actin. Platelet-mediated clot retraction in dilute platelet-rich plasma (PRP) is inhibited progressively at cytochalasin B concentrations of 0.01 mg/ml, 0.05 mg/ml and 0.1 mg/ml. Dynamic rheological measurements of recalcified PRP in a Weissenberg Rheogoniometer indicate that platelet contractility (as reflected in measurements of elastic moduli) is reduced by 33%, 57% and 63% at cytochalasin B concentrations of 0.01, 0.05 and 0.1 mg/ml, respectively. In contrast, pre-incubation of human platelet-rich plasma (PRP) with 0.01 mg/ml or 0.05 mg/ml cytochalasin B does not inhibit collagen-induced [14C]serotonin release on collagen-induced-platelet aggregation, which is dependent on the release of ADP from platelet dense granules. Even at a cytochalasin B concentration of 0.1 mg/ml, collagen-induced [14C-]serotonin release and aggregation are impaired only moderately. Cytochalasin B does not interfere with the uptake by platelets of [14C-]-serotonin, or with the kinetics and extent of clot formation in platelet-free plasma. Thus, concentrations of cytochalasin B which impair platelet contractility do not inhibit the release of platelet dense granule contents. It is concluded that neither the platelet release reaction nor platelet aggregation is dependent on platelet contractile mechanisms.
D000199:Actins / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D002417:Cattle; D003094:Collagen / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects; D005337:Fibrin; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D000199:Actins; D012701:Serotonin; D003571:Cytochalasin B; D000244:Adenosine Diphosphate; D005337:Fibrin; D003094:Collagen; D013917:Thrombin