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

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 Ca 2+ concentration ([Ca 2+ ]i) of VSMCs, which was desensitized by pretreatment with ATP, but not with 2-methylthioATP nor α,β-methyleneATP. The incubation of serum-deprived G 0 cells with platelet derived growth factor (PDGF) induced cell cycle progression into the G 1 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 G 0 cells. The incubation of the PDGF-pretreated cells at the G 1 phase with 2-methylthioATP or α,β-methyleneATP had no effect on the cell cycle of G 1 cells, while the incubation of the G 1 cells with UTP, ATP, and ATPγS stimulated cell cycle progression into the S and M phases. These results thus indicate that P 2U purinergic activation mediates a [Ca 2+ ]i transient and a progression growth factor effect of nucleotides in VSMCs.