Cytochalasin B, the blood platelet release reaction and cyclic GMP

Abstract

CYTOCHALASIN B (CB) affects a wide range of cellular processes that appear to be contractile in nature¹. The molecular mechanisms responsible for these effects are uncertain, though it is known that CB interferes with microfilament function¹ and can block transport of glucose across cell membranes^2,3. Secretion by exocytosis has been shown to be inhibited by CB in some cell types^4–8 but to be potentiated by CB in others^9–12. We describe here the effects of CB on the release reaction of blood platelets induced by collagen fibres, a process in which the contents of both amine storage granules (5-HT, ADP, ATP) and lysosomes are secreted¹³ and which leads to platelet aggregation mediated by the ADP released¹⁴. Although previous studies have shown that CB inhibits various platelet activities including clot retraction^15–17 and platelet aggregation^16,17, we now find that lower concentrations of CB markedly potentiate both the secretory activities of the platelet and release-dependent aggregation. Because collagen-induced platelet aggregation is associated with an increase in intracellular cyclic GMP¹⁸, a compound which potentiates secretion by some cells^19,20, and because it has been suggested that CB may stimulate leukotaxis by increasing cyclic GMP²¹, we have studied the relationship between the platelet release reaction and platelet cyclic GMP levels in the presence and absence of CB. The results show that CB does not potentiate the release reaction through any direct effect on cyclic GMP levels.