Nakashima J, Brookins J, Beckman B, Fisher J W
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Am J Physiol. 1991 Sep;261(3 Pt 1):C455-60. doi: 10.1152/ajpcell.1991.261.3.C455.
The present studies were undertaken to assess the direct effects of N6-cyclohexyladenosine (CHA), a stable adenosine analogue, on erythropoietin (Ep) secretion in hepatocellular carcinoma cells (Hep 3B). Ep levels in the medium of low density Hep 3B cells treated with CHA in concentrations of 10(-5) and 5 x 10(-5) M for 20 h under hypoxic conditions (1% O2) were significantly higher than that of hypoxic controls. In addition, CHA at the same concentrations produced significant increases in adenosine 3',5'-cyclic monophosphate (cAMP) levels in Hep 3B cells after 1-h incubation under hypoxic conditions when compared with hypoxic controls. Dibutyryl cAMP (10(-5), 10(-4) M) also caused significant increases in Ep secretion when compared with control hypoxic cells. On the other hand, 8-phenyltheophylline, an adenosine receptor antagonist, significantly inhibited the stimulatory effects of CHA on both Ep secretion and cAMP accumulation in the Hep 3B cell cultures in response to hypoxia. These data suggest that Ep secretion may be regulated by adenosine receptor-coupled activation of adenylyl cyclase and the generation of cAMP.
本研究旨在评估稳定的腺苷类似物N6-环己基腺苷（CHA）对肝癌细胞（Hep 3B）中促红细胞生成素（Ep）分泌的直接影响。在低氧条件（1% O2）下，用浓度为10(-5)和5×10(-5) M的CHA处理低密度Hep 3B细胞20小时，培养基中的Ep水平显著高于低氧对照组。此外，在低氧条件下孵育1小时后，与低氧对照组相比，相同浓度的CHA使Hep 3B细胞中的3',5'-环磷酸腺苷（cAMP）水平显著升高。与对照低氧细胞相比，二丁酰cAMP（10(-5)，10(-4) M）也显著增加了Ep分泌。另一方面，腺苷受体拮抗剂8-苯基茶碱显著抑制了CHA对Hep 3B细胞培养物中Ep分泌和cAMP积累的刺激作用，以应对低氧。这些数据表明，Ep分泌可能受腺苷受体偶联的腺苷酸环化酶激活和cAMP生成的调节。
