Proliferation and signaling in fibroblasts - Role of 5-hydroxytryptamine2A receptor and transporter

Welsh, D. J., Harnett, M. , Maclean, M. and Peacock, A. J. (2004) Proliferation and signaling in fibroblasts - Role of 5-hydroxytryptamine2A receptor and transporter. American Journal of Respiratory and Critical Care Medicine, 170(3), pp. 252-259. (doi:10.1164/rccm.200302-264OC)

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Publisher's URL: http://dx.doi.org/10.1016/10.1164/rccm.200302-264OC

Abstract

5-Hydroxytryptamine (5-HT) plays an important role in the remodeling of the pulmonary circulation, notably during exposure to hypoxia. Here, we have been interested in the role of 5-HT and the 5-HT 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 study has examined the effects of 5-HT 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-HT 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-HT<sub>2A</sub> receptor is responsible for the hypoxia-associated 5-HT proliferation in these cells by using specific receptor agonist and antagonist studies and that this receptor signals via p38 mitogen-activated protein kinase. We have also shown that the 5-HT transporter is important in the mitogenic response not pertaining to hypoxic stimulation. Taken together, these data suggest that 5-HT<sub>2A</sub>receptor antagonists may have a role in pulmonary artery fibroblast proliferation to hypoxia.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Harnett, Professor Margaret
Authors: Welsh, D. J., Harnett, M., Maclean, M., and Peacock, A. J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:American Journal of Respiratory and Critical Care Medicine
Publisher:American Thoracic Society
ISSN:1073-449X
ISSN (Online):1535-4970

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