Activation of P2Y2 purinoceptor inhibits the activity of the Na+/K+-ATPase in HeLa cells

The role of ATP on regulation of the Na⁺/K⁺-ATPase activity in the human cancerous HeLa cells was investigated. HeLa cells stimulated with increasing ATP concentrations showed a dose-dependent inhibition of the Na⁺/K⁺-ATPase activity. These effects were also obtained by UTP. ATP and UTP provoked a rise in intracellular calcium concentration ([Ca²⁺]_i) persisting for at least 4 min. The inhibitor of phospholipase C, U73122, blocked the elevation of [Ca²⁺]_i provoked by ATP/UTP. The expression of mRNA for P2Y2 and P2Y6 receptors was demonstrated by RT-PCR. ATP/UTP activated PKC-α, -βI and -ε isoforms, but not PKC-δ and -ζ. The inhibition of the Na⁺/K⁺-ATPase activity by ATP/UTP was blocked by Gö6976, a specific inhibitor of the calcium-dependent PKCs. In conclusion, our results suggest that ATP/UTP modulate Na⁺/K⁺-ATPase activity in HeLa cells through the P2Y2 purinoceptor via calcium mobilisation and activation of calcium-dependent PKCs.