Serotonin and pulmonary hypertension--from bench to bedside?
The serotonin hypothesis of pulmonary arterial hypertension (PAH) arose owing to anorexigens, acting as indirect serotinergic agonists, causing PAH. However, it is now thought that serotonin plays an important role in the pathobiology of PAH per se. The rate-limiting enzyme in the synthesis of peripheral serotonin is tryptophan hydroxylase 1 (TPH1), serotonin can mediate pulmonary arterial smooth muscle cell proliferation via the serotonin transporter (SERT) and serotonin can induce pulmonary vasoconstriction via the 5-HT1B receptor in man. There is evidence that TPH1, SERT and 5-HT1B expression/activity can be upregulated in clinical PAH. This review discusses recent evidence implicating serotonin in the development of experimental and clinical PAH and suggests potential therapeutic targets.
MacLean
Margaret R
MR
Integrative and Systems Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. m.maclean@bio.gla.ac.uk
Dempsie
Yvonne
Y
D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000009:adverse effects; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014661:Vasoconstriction
D044302:Receptor, Serotonin, 5-HT1B; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase