Authors: MacLean MR, Herve P, Eddahibi S, Adnot S
PMID: 10991906 PMCID: PMC1572323 DOI: 10.1038/sj.bjp.0703570
Abstract
Circulating 5-hydroxytryptamine (5-HT) is produced mainly in the enterochromaffin cells of the intestine. 5-HT is also, however, locally released from pulmonary neuroendocrine cells and neuroepithelial bodies distributed throughout the airways. Secretion of large amounts of 5-HT from these cells occurs in response to airway hypoxia and increased local 5-HT may contribute to secondary pulmonary arterial hypertension [PAH] (Johnson & Georgieff, 1989). Normally, plasma levels of free 5-HT are extremely low as circulating 5-HT is stored within the platelets. Human blood platelets contain a relatively specific uptake mechanism for 5-HT (the 5-HT transporter [5-HTT]) at the plasma membrane, intracellular storage organelles (dense bodies) and a metabolizing enzyme (monoamine oxidase B). The ‘Serotonin hypothesis of PAH’ was developed in the 1960’s after an outbreak of PAH was observed in patients taking aminorex, a diet pill that increases 5-HT availability by inducing platelet release of 5-HT, inhibiting its reuptake and inhibiting monoamine oxidase activity. Since then there has been increasing interest in the role of 5-HT in the development of PAH. Here we review pharmacological evidence 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.
Keywords: 5-hydroxytryptamine, pulmonary arterial hypertension
Source: https://pubmed.ncbi.nlm.nih.gov/10991906/
Archive: https://archive.ph/2itgp
