title: P2U purinergic activation leads to the cell cycle progression from the G1 to the S and M phases but not from the G0 to G1 phase in vascular smooth muscle cells in primary culture.
abstract: The regulation of the cell cycle by extracellular UTP was investigated in rat aortic smooth muscle cells in primary culture (VSMCs) by means of an immunocytochemical analysis of cell cycle-specific nuclear antigens. UTP induced a rise in the cytosolic Ca2+ concentration ([Ca2+]i) of VSMCs, which was desensitized by pretreatment with ATP, but not with 2-methylthioATP nor alpha, beta-methyleneATP. The incubation of serum-deprived G0 cells with platelet derived growth factor (PDGF) induced cell cycle progression into the G1 phase without any further progression into the S and M phases, while none of the nucleotides had any effect on the cell cycle of the G0 cells. The incubation of the PDGF-pretreated cells at the G1 phase with 2-methylthioATP or alpha, beta-methyleneATP had no effect on the cell cycle of G1 cells, while the incubation of the G1 cells with UTP, ATP, and ATP gamma S stimulated cell cycle progression into the S and M phases. These results thus indicate that P2U purinergic activation mediates a [Ca2+]i transient and a progression growth factor effect of nucleotides in VSMCs.
authors.affiliation: Division of Molecular Cardiology, Research Institute of Angiocardiology, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyagi
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: A
authors.initials: A
authors.lastname: Ahmed
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Fukui
authors.forename: H
authors.initials: H
authors.lastname: Kanaide
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta; D000077214:Becaplermin; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D007700:Kinetics; D008297:Male; D008938:Mitosis; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058473:Receptors, Purinergic P2Y2; D011994:Recombinant Proteins / Q000494:pharmacology; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D014544:Uridine Triphosphate / Q000494:pharmacology*
chemical_list: C546385:P2RY2 protein, human; C546387:P2ry2 protein, rat; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D011994:Recombinant Proteins; D000077214:Becaplermin; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate