Synthesis of thromboxane A2 by non-aggregating dog platelets challenged with arachidonic acid or with prostaglandin H2

Dog platelets challenged with arachidonic acid fail to aggregate but synthesize a substance which aggregates rabbit and human platelets, this aggregation being suppressed by dibutyryl cyclic AMP. The aggregating substance contracts strips of rabbit aorta and of coeliac and mesenteric arteries, is soluble in diethyl ether, has a half-life of about 40 seconds at 37°C and of 100 seconds at 22°C. Its generation is blocked by various inhibitors of prostaglandin biosynthesis. The thromboxane A₂ synthetase inhibitor imidazole and its analogue benzimidazolamine also suppress generation of vessel contracting activity in incubates of dog platelets and prostaglandin H₂. Since dog platelets also transform prostaglandin H₂ into thromboxane A₂ their failure to aggregate, when stimulated by arachidonic acid or by prostaglandin H₂, is not due to lack of thromboxane synthesizing ability.