Th serotonin hypothesis of pulmonary hypertension revisited

Margaret R MacLean, Yvonne Dempsie

Research output: Contribution to journalLiterature review

Abstract

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.
Original languageEnglish
Pages (from-to)309-22
Number of pages14
JournalAdvances in Experimental Medicine and Biology
Volume661
DOIs
Publication statusPublished - 2010

Fingerprint

Pulmonary Hypertension
Serotonin
Serotonin Plasma Membrane Transport Proteins
Constriction
Pulmonary Artery
Aminorex
Dexfenfluramine
Receptor, Serotonin, 5-HT1B
Tryptophan Hydroxylase
Appetite Depressants
rho-Associated Kinases
Extracellular Signal-Regulated MAP Kinases
Endothelial cells
Smooth Muscle Myocytes
Disease Outbreaks
Muscle
Reactive Oxygen Species
Bone
Endothelial Cells
Cells

Keywords

  • pulmonary arterial hypertension
  • serotonin
  • endothelial cells

Cite this

@article{0ecc7ddf28924a178f5a2f08b5668db4,
title = "Th serotonin hypothesis of pulmonary hypertension revisited",
abstract = "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.",
keywords = "pulmonary arterial hypertension , serotonin, endothelial cells",
author = "MacLean, {Margaret R} and Yvonne Dempsie",
year = "2010",
doi = "10.1007/978-1-60761-500-2_20",
language = "English",
volume = "661",
pages = "309--22",
journal = "Advances in Experimental Medicine and Biology",
issn = "0065-2598",
publisher = "Springer New York",

}

Th serotonin hypothesis of pulmonary hypertension revisited. / MacLean, Margaret R; Dempsie, Yvonne.

In: Advances in Experimental Medicine and Biology, Vol. 661, 2010, p. 309-22.

Research output: Contribution to journalLiterature review

TY - JOUR

T1 - Th serotonin hypothesis of pulmonary hypertension revisited

AU - MacLean, Margaret R

AU - Dempsie, Yvonne

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - pulmonary arterial hypertension

KW - serotonin

KW - endothelial cells

U2 - 10.1007/978-1-60761-500-2_20

DO - 10.1007/978-1-60761-500-2_20

M3 - Literature review

VL - 661

SP - 309

EP - 322

JO - Advances in Experimental Medicine and Biology

JF - Advances in Experimental Medicine and Biology

SN - 0065-2598

ER -