Document Detail


Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats.
MedLine Citation:
PMID:  20947677     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by vasoconstriction and remodelling of the pulmonary vasculature. The serotonin (5-hydroxytryptamine (5-HT)) pathway has been shown to play a major role in the pathogenesis of PAH, but pharmacological modulation of this pathway for treatment of PAH is, to date, at a pre-clinical level. Terguride is a 5-HT receptor (5-HTR) antagonist that is well tolerated and clinically approved for ovulation disorders. Immunohistochemistry against 5-HTR(₂A/B) on human lungs revealed their localisation to the vascular smooth muscle layer and quantitative RT-PCR showed 5-HTR(₂B) upregulation in pulmonary artery smooth muscle cells (PASMC) isolated from PAH patients. Proliferation and migration of cultured primary human PASMC were dose-dependently blocked by terguride. Therapeutic 5-HT signalling inhibition was 1) demonstrated in isolated, ventilated and perfused rat lungs and 2) by chronic terguride treatment of rats with monocrotaline (MCT)-induced pulmonary hypertension in a preventive or curative approach. Terguride inhibited proliferation of PASMCs and abolished 5-HT-induced pulmonary vasoconstriction. Chronic terguride treatment prevented dose-dependently the development and progression of MCT-induced PAH in rats. Thus, terguride represents a valuable novel therapeutic approach in PAH.
Authors:
R Dumitrascu; C Kulcke; M Königshoff; F Kouri; X Yang; N Morrell; H A Ghofrani; N Weissmann; R Reiter; W Seeger; F Grimminger; O Eickelberg; R T Schermuly; S S Pullamsetti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-14
Journal Detail:
Title:  The European respiratory journal     Volume:  37     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-08-31     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1104-18     Citation Subset:  IM    
Affiliation:
University of Giessen Lung Center, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Cell Proliferation / drug effects
Cells, Cultured
Dopamine Agonists / therapeutic use*
Female
Humans
Hypertension, Pulmonary / chemically induced,  drug therapy*,  pathology
Lisuride / analogs & derivatives*,  therapeutic use
Lung / drug effects*,  pathology,  physiopathology
Lung Transplantation
Male
Monocrotaline / pharmacology
Muscle, Smooth, Vascular / drug effects,  pathology,  physiopathology
Pulmonary Artery / drug effects,  pathology,  physiopathology
Rats
Serotonin 5-HT2 Receptor Antagonists / pharmacology*
Chemical
Reg. No./Substance:
0/Dopamine Agonists; 0/Serotonin 5-HT2 Receptor Antagonists; 18016-80-3/Lisuride; 21OJT43Q88/dironyl; 315-22-0/Monocrotaline
Comments/Corrections
Comment In:
Expert Opin Ther Targets. 2011 Nov;15(11):1333-5   [PMID:  21762037 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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