Exogenous ATP induces a limited cell cycle progression of arterial smooth muscle cells.
Because exogenous ATP is suspected to influence the proliferative process, its effects on the cell cycle progression of arterial smooth muscle cells were studied by investigating changes in the mRNA steady-state level of cell cycle-dependent genes. Stimulation of cultured quiescent smooth muscle cells by exogenous ATP induced chronological activation not only of immediate-early but also of delayed-early cell cycle-dependent genes, which were usually expressed after a mitogenic stimulation. In contrast, ATP did not increase late G1 gene mRNA level, demonstrating that this nucleotide induces a limited cell cycle progression of arterial smooth muscle cells through the G1 phase but is not able by itself to induce crossing over the G1-S boundary and consequently DNA synthesis. An increase in c-fos mRNA level was also induced by ADP but not by AMP or adenosine. Moreover, 2-methylthioadenosine 5'-triphosphate but not alpha, beta-methyleneadenosine 5'-triphosphate mediated this kind of response. Taken together, these results demonstrate that extracellular ATP induces the limited progression of arterial smooth muscle cells through the G1 phase via its fixation on P2 gamma receptors.
Malam-Souley
R
R
Unité 8 de Cardiologie, Institut National de la Santé et de la Recherche Médicale, Pessac, France.
Campan
M
M
Gadeau
A P
AP
Desgranges
C
C
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D015342:DNA Probes; D004790:Enzyme Induction; D016193:G1 Phase / Q000235:genetics; D015870:Gene Expression; D016762:Genes, fos / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D006657:Histones / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics
D015342:DNA Probes; D006657:Histones; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D013937:Thymidine Kinase; D009955:Ornithine Decarboxylase