Serotonin increases DNA synthesis in rat proximal and distal pulmonary vascular smooth muscle cells in culture

B. R. Pitt, W. Weng, A. R. Steve, R. D. Blakely, I. Reynolds, P. Davies

Research output: Contribution to journalArticlepeer-review

Abstract

Cultured smooth muscle cells obtained from rat lung periphery (RPC) and proximal pulmonary artery (RSMC) expressed mRNA for serotonin (5-HT) type 2 receptor (5-HT2) and 5-HT transporter (by Northern blot analysis). Functional expression of these genes was evident since both cell types 1) bound 125I-labeled lysergic acid diethylamide (LSD; 5-HT2 receptor antagonist) that was equally effectively displaced by either ketanserin or mianserin; and 2) transported 5-[3H]HT in an imipramine-sensitive manner. Serotonin (10-9-10-5 M) stimulated DNA synthesis (as measured by [3H]thymidine uptake) in RPC and RSMC. The 5-HT-induced increase in DNA synthesis was significantly inhibited in both cell types by the 5-HT2 receptor antagonist, ketanserin (10-7-10-6 M), and by fluoxetine (10-6 M), a putative 5-HT transport inhibitor. Acute exposure to 5-HT (1-100 μM) caused an abrupt rise in intracellular calcium ([Ca2+](i)) in single pulmonary vascular smooth muscle cells as microspectrofluorometrically determined using the calcium-sensitive dye, fura 2. The 5-HT-induced change in [Ca2+](i) was completely abolished in the presence of 10-6 M ketanserin as well as imipramine or fluoxetine (10-6 M). The calcium transients due to 5-HT persisted in a Na+-free condition (in which the transporter activity was completely abolished) and imipramine and fluoxetine (and ketanserin) were effective inhibitors of 5-HT under these conditions. Therefore, the 5-HT2 receptor, but not the transporter, is responsible for initiating the acute effects (e.g., calcium transients) of 5-HT in cultured rat pulmonary vascular smooth muscle cells and fluoxetine (1 μM) may have 5- HT2-receptor antagonist properties. These molecular and pharmacologic data are consistent with the presence of both a 5-HT2 receptor and transporter in cultured rat pulmonary vascular smooth muscle cells and suggest that 5-HT is a potential intrapulmonary growth factor.

Original languageEnglish (US)
Pages (from-to)L178-L186
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume266
Issue number2 10-2
DOIs
StatePublished - 1994

Keywords

  • growth factors
  • intracellular calcium
  • pulmonary pericyte

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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