细胞外ATP对HL-60细胞的生长抑制作用：P2受体和腺苷生成的浓度依赖性参与
Growth inhibition of HL-60 cells by extracellular ATP: concentration-dependent involvement of a P2 receptor and adenosine generation.
作者信息
Seetulsingh-Goorah S P, Stewart B W
机构信息
Children's Cancer Research Institute, Sydney Children's Hospital, Randwick, NSW, Australia.
出版信息
Biochem Biophys Res Commun. 1998 Sep 18;250(2):390-6. doi: 10.1006/bbrc.1998.9329.
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.
向HL-60细胞培养物中单次添加ATP（20 - 1000微摩尔）可导致细胞增殖受到永久性的、不依赖钙离子的抑制，在处理后48小时即可明显观察到。细胞外ATP（ATPo）在250微摩尔时效果最佳，可使细胞生长抑制率达到90 ± 1.5%。在ATPo浓度达到250微摩尔之前，生长抑制完全归因于ATPo，而在更高的ATPo浓度下，ATPo水解产生的腺苷也对这种效应有贡献。生长抑制的效力顺序为ATP = ADP > AMP > 腺苷。苏拉明，一种P2受体拮抗剂，可减弱ATP和ADP对生长的抑制作用，表明P2受体参与其中。ATP和ADP的等效性排除了胞外蛋白激酶或P2X7受体参与生长抑制的可能性。UTP（P2Y2激动剂）和α,β - 亚甲基ATP（P2X1激动剂）均未抑制生长，表明这种抑制是由HL-60细胞上一种先前未描述的P2受体介导的。
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