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 2A 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 selective 5-HT2A receptor antagonists may have a role in pulmonary artery fibroblast proliferation to hypoxia.
Original language | English |
---|---|
Pages (from-to) | 252-259 |
Number of pages | 8 |
Journal | American Journal of Respiratory and Critical Care Medicine |
Volume | 170 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Aug 2004 |
Keywords
- 5-hydroxytryptamine
- fibroblasts
- hypoxia
- pulmonary
- pulmonary hypertension
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine