Document Detail


Protease-activated receptor (PAR) 1 but not PAR2 or PAR4 mediates endothelium-dependent relaxation to thrombin and trypsin in human pulmonary arteries.
MedLine Citation:
PMID:  11444493     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelial protease-activated receptors (PARs) may be important sensors of vascular inflammation and injury. Activation of endothelial PAR1 and PAR2 causes nitric oxide-mediated arterial smooth muscle relaxation in a number of species and PAR4 activation causes similar responses in isolated rat aorta. However, it is unclear whether these receptors mediate such responses in human arteries because the most potent activators of PAR1, PAR2, and PAR4, thrombin and trypsin, cause endothelium-dependent relaxation of human coronary arteries through a common PAR1-like receptor. This study aimed to determine whether this unique pharmacology of PARs in human coronary arteries extends to human pulmonary arteries. PAR1 and PAR2 mRNA and protein were detected in human pulmonary arteries via reverse transcription polymerase chain reaction and immunohistochemistry, respectively. PAR4 mRNA was also detected in human pulmonary arteries. Contracted human pulmonary artery ring segments suspended for isometric tension measurement relaxed in a concentration- and endothelium-dependent manner to thrombin (0.001-0.1 U/ml), trypsin (0.01-1 U/ml), and the PAR1-activating peptide, SFLLRN (0.1-10 microM). By contrast, the PAR2- and PAR4-activating peptides, SLIGKV and GYPGQV, respectively, caused neither contraction nor relaxation of precontracted human pulmonary arteries. Relaxations to thrombin and trypsin cross-desensitized, while tachyphylaxis to SFLLRN abolished subsequent relaxations to both thrombin and trypsin. We conclude that human pulmonary arteries express PAR1, PAR2, and PAR4, but that only PAR1, or a PAR1-like receptor, is coupled to endothelium-dependent relaxation.
Authors:
J R Hamilton; J D Moffatt; A G Frauman; T M Cocks
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  38     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-07-10     Completed Date:  2001-12-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  108-19     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Melbourne, Victoria, Australia.
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MeSH Terms
Descriptor/Qualifier:
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects*,  physiology
Female
Hemostatics / pharmacology*
Humans
Male
Middle Aged
Pulmonary Artery / drug effects*,  physiology
Receptor, PAR-1
Receptor, PAR-2
Receptors, Thrombin / physiology*
Thrombin / pharmacology*
Trypsin / pharmacology*
Vasodilation / drug effects*,  physiology
Chemical
Reg. No./Substance:
0/Hemostatics; 0/Receptor, PAR-1; 0/Receptor, PAR-2; 0/Receptors, Thrombin; 0/protease-activated receptor 4; EC 3.4.21.4/Trypsin; EC 3.4.21.5/Thrombin

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


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