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 synergistically elevated cytosolic free Ca2+ concentration ([Ca2+]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 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-HT2 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 Ca2+. 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.
Roevens
P
P
Department of Biochemistry II, Janssen Research Foundation, Beerse, Belgium.
De Clerck
F
F
de Chaffoy de Courcelles
D
D
D000244:Adenosine Diphosphate / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000097:blood / Q000378:metabolism*
D012701:Serotonin; D000244:Adenosine Diphosphate; D007650:Ketanserin; D010738:Type C Phospholipases; D002118:Calcium; D004837:Epinephrine