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Published on: February 15, 2022
Serotonin induces pulmonary artery smooth muscle cell migration
Regina M Day1, Abena S Agyeman, Michael J Segel
1Department of Pharmacology, The Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA. rday@usuhs.mil
Biochemical Pharmacology
|December 1, 2005
Summary
Serotonin (5-hydroxytryptamine, 5-HT) significantly increases pulmonary artery smooth muscle cell (PASMC) migration and actin reorganization. This process is mediated by the 5-HT4 receptor, cyclic AMP (cAMP), and chloride channels, contributing to pulmonary vascular remodeling.
Area of Science:
- Cardiovascular Biology
- Cellular Physiology
- Molecular Medicine
Background:
- Pulmonary arterial hypertension (PAH) involves vascular remodeling, characterized by smooth muscle thickening in pulmonary arteries.
- Serotonin (5-hydroxytryptamine, 5-HT) is implicated in pulmonary artery smooth muscle cell (PASMC) proliferation, hypertrophy, and potentially vascular remodeling.
- Previous research indicates 5-HT induces morphological changes in PASMC via cyclic AMP (cAMP).
Purpose of the Study:
- To investigate the role of serotonin (5-HT) in stimulating pulmonary artery smooth muscle cell (PASMC) migration.
- To elucidate the signaling pathways, including the 5-HT4 receptor, cAMP, and chloride channels, involved in 5-HT-induced PASMC migration and cytoskeletal changes.
Main Methods:
- Utilized a modified Boyden chamber assay to quantify PASMC migration in response to 5-HT.
- Assessed cellular morphology and actin cytoskeleton reorganization.
- Investigated the involvement of the 5-HT4 receptor, cAMP, and chloride channels using specific antagonists and blockers.
Main Results:
- 5-HT treatment increased PASMC migration up to four-fold.
- Increased migration was associated with cellular morphological changes and actin cytoskeleton reorganization.
- 5-HT4 receptor and cAMP antagonists, along with a chloride channel blocker, significantly inhibited 5-HT-induced migration and cytoskeletal changes.
Conclusions:
- Serotonin (5-HT) stimulates PASMC migration and actin cytoskeletal reorganization.
- This effect is mediated through the 5-HT4 receptor and subsequent cAMP activation of a chloride channel.
- These findings highlight a potential mechanism contributing to pulmonary vascular remodeling in PAH.
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