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 ([Ca(2+)](i)) persisting for at least 4 min. The inhibitor of phospholipase C, U73122, blocked the elevation of [Ca(2+)](i) provoked by ATP/UTP. The expression of mRNA for P2Y2 and P2Y6 receptors was demonstrated by RT-PCR. ATP/UTP activated PKC-alpha, -betaI and -epsilon isoforms, but not PKC-delta and -zeta. 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.
Muscella
Antonella
A
Department of Biological Sciences and Environmental Technology (DisTeBA), Laboratory of Cell Physiology, University of Lecce, Ecotekne, Via Provinciale per Monteroni, 73100 Lecce, Italy.
Elia
Maria Giovanna
MG
Greco
Simona
S
Storelli
Carlo
C
Marsigliante
Santo
S
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
C546385:P2RY2 protein, human; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium