Publication
Title
Knockout mice reveal a role for receptor in macrophages, endothelial cells, and vascular smooth muscle cells
Author
Abstract
P2Y receptors are G-protein-coupled receptors activated by extracellular nucleotides. The P2Y6 receptor is selectively activated by UDP, and its transcript has been detected in numerous organs, including the spleen, thymus, intestine, blood leukocytes, and aorta. To investigate the biological functions of this receptor, we generated P2Y6-null mice by gene targeting. The P2Y6 knockout (KO) mice are viable and are not distinguishable from the wild-type (WT) mice in terms of growth or fertility. In thioglycollate-elicited macrophages, the production of inositol phosphate in response to UDP stimulation was lost, indicating that P2Y6 is the unique UDP-responsive receptor expressed by mouse macrophages. Furthermore, the amount of interleukin-6 and macrophage-inflammatory protein-2, but not tumor necrosis factor-, released in response to lipopolysaccharide stimulation was significantly enhanced in the presence of UDP, and this effect was lost in the P2Y6 KO macrophages. The endothelium-dependent relaxation of the aorta by UDP was abolished in KO P2Y6 mice. The contractile effect of UDP on the aorta, observed when endothelial nitric-oxide synthase is blocked, was also abolished in P2Y6-null mice. In conclusion, we generated P2Y6-deficient mice and have shown that these mice have a defective response to UDP in macrophages, endothelial cells, and vascular smooth muscle cells. These observations might be relevant to several physiopathological conditions such as atherosclerosis or hypertension.
Language
English
Source (journal)
Molecular pharmacology. - Bethesda, Md
Publication
Bethesda, Md : 2008
ISSN
0026-895X
Volume/pages
74:3(2008), p. 777-784
ISI
000258637500024
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 27.05.2009
Last edited 18.06.2017
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