Pulmonary hypertension: therapeutic targets within the serotonin system

Dempsie, Y. and MacLean, M.R. (2008) Pulmonary hypertension: therapeutic targets within the serotonin system. British Journal of Pharmacology, 155(4), pp. 455-462. (doi: 10.1038/bjp.2008.241)

Abstract

Pulmonary arterial hypertension (PAH) is characterized by a sustained and progressive elevation in pulmonary arterial pressure and pulmonary vascular remodelling leading to right heart failure and death. Prognosis is poor and novel therapeutic approaches are needed. The serotonin hypothesis of PAH originated in the 1960s after an outbreak of the disease was reported among patients taking the anorexigenic drugs aminorex and fenfluramine. These are indirect serotinergic agonists and serotonin transporter substrates. Since then many advances have been made in our understanding of the role of serotonin in the pathobiology of PAH. The rate-limiting enzyme in the synthesis of serotonin is tryprophan hydroxylase (Tph). Serotonin is synthesized, through Tph1, in the endothelial cells of the pulmonary artery and can then act on underlying pulmonary arterial smooth muscle cells and pulmonary arterial fibroblasts in a paracrine fashion causing constriction and remodelling. These effects of serotonin can be mediated through both the serotonin transporter and serotonin receptors. This review will discuss our current understanding of 'the serotonin hypothesis' of PAH and highlight possible therapeutic targets within the serotonin system.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacLean, Professor Margaret and Dempsie, Dr Yvonne
• Authors: Dempsie, Y., and MacLean, M.R.
• Subjects: R Medicine > RC Internal medicine
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences
• Journal Name: British Journal of Pharmacology
• ISSN: 0007-1188