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Nucleotide receptor P 2u partially mediates ATP‐induced cell cycle progression of aortic smooth muscle cells
Author(s) -
MalamSouley Rabé,
Seye Cheikh,
Gadeau AlainPierre,
Loirand Gervaise,
Pillois Xavier,
Campan Michel,
Pacaud Pierre,
Desgranges Claude
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199601)166:1<57::aid-jcp7>3.0.co;2-f
Subject(s) - microbiology and biotechnology , purinergic receptor , biology , receptor , vascular smooth muscle , intracellular , chemotaxis , extracellular , cell cycle , cell , endocrinology , biochemistry , smooth muscle
mRNA of the P 2u purinoceptor (or nucleotide receptor) is detected both by polymerase chain reaction or Northern blot analyses in cultured aortic smooth muscle cells. When added to the culture medium of these cells, UTP, a specific ligand of the P 2u receptor, induces an increased expression of both immediate‐early and delayed‐early cell cycle‐dependent genes. This induction demonstrates similar features (kinetics, concentration dependence) to those obtained after stimulation of aortic smooth cells by exogenous ATP, a common ligand for most P 2 purinoceptors. In contrast, 2‐methylthioATP, a preferential ligand for P 2γ purinoceptors, induces only a significant increase of immediate‐early genes but not of delayed‐early genes. Moreover, the 2‐methylthioATP‐induced responses (c‐fos mRNA increase, free intracellular calcium transient) are lower than those induced by ATP or UTP and are complementary to those of UTP. These results demonstrate that functional P 2u receptors are present on cultured aortic smooth muscle cells and suggest that the bulk of responses induced by extracellular ATP on cell cycle progression are mediated via P 2u purinoceptors, a hypothesis confirmed by cytofluorometric studies. Since some ATP‐or UTP‐induced genes code for chemotactic proteins (monocyte chemoattractant protein‐1 and osteopontin), this study suggests that these nucleotides may contribute to vascular or blood cell migration and proliferation and consequently to the genesis of arterial diseases. © 1996 Wiley‐Liss, Inc.