The synergistic effect of 5-hydroxytryptamine and epinephrine on the human platelet is related to the activation of phospholipase C

Abstract Simultaneous addition of 5-hydroxytryptamine (5-HT) and epinephrine synergistically elevated cytosolic free Ca 2+ concentration ([Ca 2+ ] cyt ) and activated phospholipase C. These phenomena occurred in an agonist concentration-dependent manner and reflected an increase in maximal response rather than a, shift in affinity for either of the stimuli. Ketanserin, a 5HT 2 receptor antagonist completely blocked the response of 5-HT plus epinephrine and this in the nanomolar concentration range in which the drug selectively antagonizes 5-HT 2 receptor-mediated responses. The synergistic effect was not a consequence of the activation by the platelet-release products ADP and 5-HT nor of influx of extracellular Ca 2+ . It is concluded that an increased activation of phospholipase C plays a major role in provoking the synergistic effects between 5-HT and epinephrine at the level of signal transduction.