Growth inhibition of HL-60 cells by extracellular ATP: concentration-dependent involvement of a P2 receptor and adenosine generation.

A single addition of ATP (20-1000 microM) to cultures of HL-60 cells resulted here in permanent, Ca(2+)-independent inhibition of cellular proliferation, evident 48 h following treatment. Extracellular ATP (ATPo) was maximally effective at 250 microM giving 90 +/- 1.5% growth inhibition. Up to a concentration of 250 microM ATPo, growth inhibition is solely attributable to ATPo, while at higher ATPo concentrations adenosine generated from ATPo hydrolysis contributes to this effect. The order of potency for growth inhibition was ATP = ADP > AMP > adenosine. Suramin, a P2 receptor antagonist, attenuated growth inhibition by ATP and ADP, indicative of P2 receptor involvement. Equipotency of ATP and ADP excludes the involvement of either an ecto-protein kinase or a P2X7 receptor in growth inhibition. Neither UTP (P2Y2 agonist) nor alpha, beta-methyleneATP (P2X1 agonist) inhibited growth, indicating that such inhibition is mediated by a previously undescribed P2 receptor on HL-60 cells.