Effects of 5-Hydroxytryptamine Class 2 Receptor Antagonists on Bronchoconstriction and Pulmonary Remodeling Processes.
Am J Pathol
; 188(5): 1113-1119, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29454752
ABSTRACT
Serotonin [5-hydroxytryptamine (5-HT)] is associated with several chronic pulmonary diseases, recognizing 5-HT2 receptor antagonists as potential inhibitors of tissue remodeling. However, the effects of 5-HT2 receptors, especially 5-HT2B receptors on airway function and remodeling, are unclear. We investigated the role of 5-HT2B receptors on airway smooth muscle contractility and remodeling processes. Murine precision-cut lung slices were pretreated with 5-HT2B receptor antagonists (EXT5, EXT9, RS 127445, and PRX 08066), as well as ketanserin (5-HT2A/2C receptor antagonist) (1, 10 µmol/L), before addition of cumulative concentrations of 5-HT to induce bronchoconstriction. Remodeling effects after treatment with 10 µmol/L 5-HT and 5-HT2 receptor antagonists were further studied in distal lung tissue by examining release of profibrotic transforming growth factor (TGF)-ß1 and proliferation of human bronchial smooth muscle cells (HBSMCs). 5-HT-induced bronchoconstriction was significantly reduced by EXT5, EXT9, and ketanserin, but not by RS 127445 or PRX 08066. The 5-HT2B receptor antagonists significantly reduced TGF-ß1 release. 5-HT, in combination with TGF-ß1, increased proliferation of HBSMCs, a process reduced by EXT5 and EXT9. Our results indicate that EXT5 and EXT9 may relieve bronchoconstriction in murine airways and serve as an add-on effect in attenuating pulmonary remodeling by improving airway function. The antiproliferative effect on HBSMCs and the inhibition of TGF-ß1 release further support a role of 5-HT2B receptors in pathologic remodeling processes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bronchoconstriction
/
Myocytes, Smooth Muscle
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Serotonin 5-HT2 Receptor Antagonists
/
Lung
Limits:
Animals
/
Humans
Language:
En
Journal:
Am J Pathol
Year:
2018
Document type:
Article