Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension

  title={Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension},
  author={Jean Marie Launay and Philippe Herv{\'e} and Katell Peoc’h and Claire Tournois and Jacques Callebert and Canan G. Nebigil and Nelly Etienne and Ludovic Drouet and Marc Humbert and G{\'e}rald Simonneau and Luc Maroteaux},
  journal={Nature Medicine},
Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT2B) receptor agonist. Thus, we investigated the contribution of the 5-HT2B receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic… 

Evidence for a Control of Plasma Serotonin Levels by 5-Hydroxytryptamine2B Receptors in Mice

The data support the notion that a 5-HT2B receptor-dependent regulation of serotonin uptake is implicated in the control of plasma serotonin levels, and provide in vivo evidence that an acute agonist stimulation of 5- HT2B receptors triggers a transient increase in plasma serotonin.

The Serotonin System as a Therapeutic Target in Pulmonary Hypertension

Severe alterations in several critical steps of this pathway have been found during the progression of PH, including changes in 5-HT synthesis and bioavailability, changes in5-HT-mediating effects on target cells, and alterations in intracellular signaling.

Expression of the serotonin 1b receptor in experimental pulmonary hypertension

The present authors conclude that this early pulmonary arterial hypertension model is characterised by an endothelin receptor-dependent increased expression of the serotonin 1B receptor, which was partially prevented by bosentan therapy.

Overexpression of the 5-Hydroxytryptamine Transporter Gene: Effect on Pulmonary Hemodynamics and Hypoxia-Induced Pulmonary Hypertension

Pulmonary hemodynamics and the development of hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in mice overexpressing the gene for the 5-HT transporter are investigated, providing a unique model that demonstrates differential mechanisms for familial pulmonary arterial hypertension and lungs with hypoxemia.

Tryptophan hydroxylase 1 Inhibition Impacts Pulmonary Vascular Remodeling in Two Rat Models of Pulmonary Hypertension

Investigation of the chronic effects of pharmacological inhibition of tryptophan hydroxylase 1 (TPH1) in two preclinical models of pulmonary hypertension demonstrates that in addition to reducing vascular remodeling, TPH1 inhibition has the added benefit of reducing the perivascular mast cell accumulation associated with PH.

Response to overexpression of 5-hydroxytryptamine 2B receptor gene in pulmonary hypertension: still a long way to understand its transcriptional regulation.

Treatment with rosiglitazone, the peroxisome proliferator-activated receptor γ (PPARγ) agonist is able to attenuate 5-hydroxytryptamine (5-HT)-induced vasoconstriction of pulmonary arteries from monocrotaline- or hypoxia-treated rats and decreases the expression of serotonin receptor 2B, suggesting a potential mechanism for the benefit of PPARγ ligands in PAH.

Evaluation of the serotonin receptor blockers ketanserin and methiothepin on the pulmonary hypertensive responses of broilers to intravenously infused serotonin.

Methiothepin will be a useful tool for evaluating the role of 5-HT in the pathogenesis of pulmonary hypertension syndrome (ascites) as well as the onset of pulmonary hypertensive triggered by inflammatory stimuli such as bacterial lipolysaccharide.

Serotonin transporter inhibitors protect against hypoxic pulmonary hypertension.

Data indicate that 5-HTT plays a key role in hypoxia-induced pulmonary vascular remodeling and the effects of serotonin transporter inhibitors on PH in humans deserve investigation.

Transglutaminase 2-mediated serotonylation in pulmonary hypertension.

  • K. PenumatsaB. Fanburg
  • Biology, Chemistry
    American journal of physiology. Lung cellular and molecular physiology
  • 2014
The present review has tried to address the current understanding of 5-HT metabolism in pulmonary hypertension and relate it to what is currently known about the evolving cellular process of serotonylation.

Pulmonary vascular effects of serotonin and selective serotonin reuptake inhibitors in the late-gestation ovine fetus.

5-HT causes pulmonary vasoconstriction, contributes to maintenance of high PVR in the normal fetus through stimulation of 5-HT 2A receptors and Rho kinase activation, and mediates the hypertensive effects of SSRIs.



Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene.

It is reported that mice deficient for 5-HTT (5-HTt(-/-)) developed less hypoxic pulmonary hypertension and vascular remodeling than paired 5- HTT(+/+) controls, and this data further support a key role of 5-htT in hypoxia-induced pulmonary vascular SMC proliferation and pulmonary hypertension.

Contribution of the 5-HT1B Receptor to Hypoxia-Induced Pulmonary Hypertension: Converging Evidence Using 5-HT1B-Receptor Knockout Mice and the 5-HT1B/1D-Receptor Antagonist GR127935

The 5-HT1B receptor plays a role in the development of CHPHT, and one possible mechanism may be via enhanced 5- HT1 receptor-mediated contraction of the pulmonary arterial circulation.

5‐hydroxytryptamine and the pulmonary circulation: receptors, transporters and relevance to pulmonary arterial hypertension

Pharmacological evidence is reviewed that suggests changes in 5-HT availability,5-HT-induced vasoconstriction, 5-ht-induced mitogenesis and 5- HT transporter activity are associated with the development of PAH.

Dexfenfluramine-associated changes in 5-hydroxytryptamine transporter expression and development of hypoxic pulmonary hypertension in rats.

Data show that, in rats, the increased 5-HTT expression that follows dexfenfluramine discontinuation promotes the development of hypoxic pulmonary hypertension.

Pulmonary hypertension, anorexigens and 5-HT: pharmacological synergism in action?

  • M. Maclean
  • Biology, Medicine
    Trends in pharmacological sciences
  • 1999

Role of serotonin in the pathogenesis of acute and chronic pulmonary hypertension

The main importance of severe pulmonary hypertension is that it may cause right ventricular dysfunction and ultimately death from right heart failure and in those with chronic obstructive pulmonary disease (COPD).

Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension.

It is concluded that 5-HTT activity plays a key role in the pathogenesis of PA-SMC proliferation in PPH and that a 5HTT polymorphism confers susceptibility to PPH.

Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling.

The results indicate that PGI(2) and its receptor play an important role in the regulation of hypoxia-induced pulmonary vascular remodeling, and that the absence of a functional receptor worsens pulmonary hypertension.

Increased plasma serotonin in primary pulmonary hypertension.

High Plasma Serotonin Levels in Primary Pulmonary Hypertension: Effect of Long-Term Epoprostenol (Prostacyclin) Therapy

The glycoprotein profile indicates that the platelets of P PH patients were not highly activated but had an accelerated turnover and returned to normal under epoprostenol treatment without change of the elevated plasma serotonin, characteristic of PPH.