Kohno Y, Sei Y, Koshiba M, Kim H O, Jacobson K A
Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Biochem Biophys Res Commun. 1996 Feb 27;219(3):904-10. doi: 10.1006/bbrc.1996.0331.
The effects of adenosine (ADO) analogs on cells of the human promyelocytic HL-60 line were examined. ADO A(3) receptor agonists, N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA, 30-60 microM) and 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (CI-IB-MECA, 10-30 microM) induced apoptotic cell death. In contrast, neither an A(1)/A(2) antagonist (XAC) nor other selective ADO receptor agonists (CPA, NECA and CGS21680) induced apoptosis at concentrations of <30 microM. Both IB-MECA and CI-IB-MECA significantly induced Ca(2+) release from intracellular Ca(2+) pools followed by Ca(2+) influx, suggesting the presence of phospholipase C-coupled ADO A(3) receptors on HL-60 cells. This was further supported by the presence of mRNA of ADO A3 receptor in the cells. These results suggest that activation of ADO A(3) receptors is responsible for the ADO-induced apoptosis in HL-60 cells and could be of potential therapeutic value in the treatment of leukemia.
研究了腺苷（ADO）类似物对人早幼粒细胞HL-60系细胞的影响。ADO A(3)受体激动剂N(6)-(3-碘苄基)腺苷-5'-N-甲基羧酰胺（IB-MECA，30 - 60微摩尔）和2-氯-N(6)-(3-碘苄基)腺苷-5'-N-甲基脲酰胺（CI-IB-MECA，10 - 30微摩尔）诱导细胞凋亡。相比之下，在浓度<30微摩尔时，A(1)/A(2)拮抗剂（XAC）以及其他选择性ADO受体激动剂（CPA、NECA和CGS21680）均未诱导细胞凋亡。IB-MECA和CI-IB-MECA均显著诱导细胞内Ca(2+)库释放Ca(2+)，随后Ca(2+)内流，提示HL-60细胞上存在与磷脂酶C偶联的ADO A(3)受体。细胞中存在ADO A3受体的mRNA进一步支持了这一点。这些结果表明，ADO A(3)受体的激活是HL-60细胞中ADO诱导凋亡的原因，在白血病治疗中可能具有潜在的治疗价值。
