The serotonin hypothesis of pulmonary hypertension revisited

MacLean, M. R. and Dempsie, Y. (2010) The serotonin hypothesis of pulmonary hypertension revisited. In: Membrane Receptors, Channels and Transporters in Pulmonary Circulation. Series: Advances in experimental medicine and biology ;; v. 661, 661. Humana Press: New York, pp. 309-322. ISBN 9781607614999 (doi: 10.1007/978-1-60761-500-2_20)

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The serotonin hypothesis of pulmonary arterial hypertension (PAH) arose after an outbreak of PAH in patients taking the anorexigenic drugs aminorex and dexfenfluramine. Both of these drugs are serotonin transporter (SERT) substrates and indirect serotinergic agonists. There is now a wealth of evidence to support a role for serotonin in the pathobiology of PAH. Synthesis of serotonin can occur in pulmonary artery endothelial cells by the enzyme tryptophan hydroxylase 1 (TPH1). Serotonin then acts at the 5-HT1B receptor and the SERT to mediate constriction and proliferation of pulmonary artery smooth muscle cells. Downstream signalling molecules which play a role in serotonin-induced constriction and proliferation include reactive oxygen species (ROS), Rho-kinase (ROCK) p38 and extracellular signal-regulated kinase (ERK). There is also evidence to suggest that serotonin may interact with the bone morphogenetic receptor type II (BMPRII) to provide a ‘second hit’ risk factor for PAH.

Item Type:Book Sections
Glasgow Author(s) Enlighten ID:MacLean, Professor Margaret and Dempsie, Dr Yvonne
Authors: MacLean, M. R., and Dempsie, Y.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Publisher:Humana Press
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
490991Effect of oestrogen on the serotonin system: role in the development of pulmonary hypertensionMargaret MacLeanMedical Research Council (MRC)G0801171Institute of Cardiovascular and Medical Sciences