Published ahead of print on April 15, 2004, doi:10.1164/rccm.200302-264OC
Am. J. Respir. Crit. Care Med., Volume 170, Number 3, August 2004, 252-259
A more recent version of this article appeared on August 1, 2004
Submitted on February 24, 2003
Accepted on April 13, 2004
Proliferation and Signalling in Fibroblasts: Role of 5-Hydroxytryptamine2A Receptor and Transporter
David J Welsh1*, Margaret Harnett2, Margaret MacLean3, and Andrew J Peacock1
1 Scottish Pulmonary Vascular Unit, Western Infirmary, Glasgow, Scotland, United Kingdom,
2 Department of Immunology, Western Infirmary, Glasgow, Scotland, United Kingdom,
3 Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom
* To whom correspondence should be addressed. E-mail: david.welsh{at}bio.gla.ac.uk.
5-hydroxytryptamine plays an important role in the remodelling of the pulmonary circulation, notably during exposure to hypoxia. Here, we have been interested in the role of 5-hydroxytryptamine and the 5-hydroxytryptamine transporter in the proliferation of pulmonary artery fibroblasts derived from pulmonary hypertensive animals, and particularly in defining which receptor subtype is of importance and in identifying a possible mechanism of this effect. This present study has examined the effects of 5-hydroxytryptamine on the proliferation and activation of Mitogen Activated Protein kinases in rat pulmonary artery fibroblasts from control and chronically hypoxic animals. We have shown that 5-hydroxytryptamine has a co-mitogenic effect with serum, to produce an enhanced proliferative response in cells from chronically hypoxic rats over those from control animals. Moreover we have found that the 5-hydroxytryptamine2A receptor is responsible for the hypoxia associated 5-hydroxytryptamine proliferation in these cells by utilising specific receptor agonist and antagonist studies, and that this receptor signals via p38 Mitogen Activated Protein kinase. We have also shown that the 5-hydroxytryptamine transporter is important in the mitogenic response not pertaining to hypoxic stimulation. Taken together, these data suggest that selective 5-hydroxytryptamine2A receptor antagonists may have a role in pulmonary artery fibroblast proliferation to hypoxia.
Key words: Hypoxia, Pulmonary hypertension, 5-HT, Fibroblasts, Pulmonary
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