Title
Knockout mice reveal a role for <tex>$P2Y_{6}$</tex> receptor in macrophages, endothelial cells, and vascular smooth muscle cells Knockout mice reveal a role for <tex>$P2Y_{6}$</tex> receptor in macrophages, endothelial cells, and vascular smooth muscle cells
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Bethesda, Md ,
Subject
Pharmacology. Therapy
Source (journal)
Molecular pharmacology. - Bethesda, Md
Volume/pages
74(2008) :3 , p. 777-784
ISSN
0026-895X
ISI
000258637500024
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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.
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