THE SYNERGISTIC EFFECT OF 5-HYDROXYTRYPTAMINE AND EPINEPHRINE ON THE HUMAN PLATELET IS RELATED TO THE ACTIVATION OF PHOSPHOLIPASE-C

Simultaneous addition of 5-hydroxytryptamine (5-HT) and epinephrine sy nergistically elevated cytosolic free Ca2+ concentration ([Ca2+]cyt) a nd activated phospholipase C. These phenomena occurred in an agonist c oncentration-dependent manner and reflected an increase in maximal res ponse rather than a, shift in affinity for either of the stimuli. Keta nserin, a 5HT2 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, receptor-mediated respon ses. The synergistic effect was not a consequence of the activation by the platelet-release products ADP and 5-HT nor of influx of extracell ular Ca2+. It is concluded that an increased activation of phospholipa se C plays a major role in provoking the synergistic effects between 5 -HT and epinephrine at the level of signal transduction.