Serotonin Signaling in Pulmonary Hypertension

Mark de Caestecker S erotonin (5-HT, 5-hydroxytryptamine) has long been recognized as one of the most potent naturally occurring pulmonary vasoconstrictors. 1 It was first implicated in the pathogenesis of pulmonary arterial hypertension (PAH) after an outbreak of the disease in Switzerland in the 1960's among patients taking aminorex fumarate, an appetite suppressant that inhibits serotonin uptake by platelets.2 Since that time further outbreaks of PAH have been identified in Europe and the USA associated with the use of fenfluraminederivate anorexigens, 3-5 eventually leading to their withdrawal from the world market in 1997.Although this was, at least in retrospect, a predictable tragedy, it has ironically opened avenues of research into the biology of serotonin signaling in PAH.As fenfluramine-derivatives are substrates for the serotonin transporter (5-HTT, SERT) proteins, 6 this suggests that abnormal SERT expression or functional activity could play a role in the pathogenesis of PAH.There is now