Proliferation and signaling in fibroblasts: role of 5- hydroxytryptamine2a receptor and transporter

David J. Welsh*, Margaret Harnett, Margaret MacLean, Andrew J. Peacock

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

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 languageEnglish
Pages (from-to)252-259
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume170
Issue number3
DOIs
Publication statusPublished - 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

Fingerprint

Dive into the research topics of 'Proliferation and signaling in fibroblasts: role of 5- hydroxytryptamine2a receptor and transporter'. Together they form a unique fingerprint.

Cite this