Bang B E, Ericsen C, Aarbakke J
Department of Pharmacology, University of Tromsø, Norway.
Pharmacol Toxicol. 1994 Aug;75(2):108-12. doi: 10.1111/j.1600-0773.1994.tb00331.x.
Previous studies have demonstrated low percentage of HL-60 cell differentiation with theophylline. The present study demonstrate that millimolar concentrations of the non-selective phosphodiesterase inhibitors theophylline, caffeine and isobutyl-methylxanthine all inhibit growth, induce substantial differentiation and elevation of both cAMP and cGMP in HL-60 cells. Selective inhibition of cAMP hydrolysis by Ro20-1724 was without effect. The guanylate cyclase stimulator sodium nitroprusside, which increased cGMP only poorly and also increased cAMP, produced growth inhibition but no differentiation. We put forward the hypothesis that elevation of both cAMP and cGMP above a critical level is necessary for significant cyclic nucleotide induced HL-60 cell differentiation.
先前的研究表明，茶碱诱导HL-60细胞分化的比例较低。本研究表明，毫摩尔浓度的非选择性磷酸二酯酶抑制剂茶碱、咖啡因和异丁基甲基黄嘌呤均能抑制HL-60细胞生长，诱导细胞大量分化，并使细胞内cAMP和cGMP水平升高。Ro20-1724对cAMP水解的选择性抑制无效。鸟苷酸环化酶刺激剂硝普钠仅能微弱增加cGMP且同时增加cAMP，可抑制细胞生长但不诱导分化。我们提出假说：cAMP和cGMP水平升高至临界水平以上对于环核苷酸诱导HL-60细胞显著分化是必要的。
