Document Detail

The serotonin hypothesis of pulmonary hypertension revisited.
MedLine Citation:
PMID:  20204739     Owner:  NLM     Status:  MEDLINE    
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-HT(1B) 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.
Margaret R Maclean; Yvonne Dempsie
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Advances in experimental medicine and biology     Volume:  661     ISSN:  0065-2598     ISO Abbreviation:  Adv. Exp. Med. Biol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-05     Completed Date:  2010-04-26     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  309-22     Citation Subset:  IM    
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MeSH Terms
Appetite Depressants / adverse effects,  metabolism
Bone Morphogenetic Protein Receptors, Type II / genetics,  metabolism
Dexfenfluramine / adverse effects,  metabolism
Endothelial Cells / cytology,  metabolism
Hypertension, Pulmonary / chemically induced,  physiopathology*
Lung / blood supply,  metabolism,  pathology
Receptors, Serotonin / metabolism
Serotonin / metabolism*
Serotonin Plasma Membrane Transport Proteins / metabolism
Serotonin Receptor Agonists / adverse effects,  metabolism
Signal Transduction / physiology
Vasoconstriction / physiology
Grant Support
G0801171//Medical Research Council
Reg. No./Substance:
0/Appetite Depressants; 0/Receptors, Serotonin; 0/Serotonin Plasma Membrane Transport Proteins; 0/Serotonin Receptor Agonists; 333DO1RDJY/Serotonin; E35R3G56OV/Dexfenfluramine; EC Morphogenetic Protein Receptors, Type II

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