Estradiol inhibits smooth muscle cell growth in part by activating the cAMP-adenosine pathway
Estradiol inhibits smooth muscle cell growth in part by activating the cAMP-adenosine pathway
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DOI：
10.1161/01.hyp.35.1.262
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发表时间：
2000-01-01
期刊：
影响因子：
8.3
通讯作者：
Jackson, EK
中科院分区：
文献类型：
--
作者：
Dubey, RK;Gillespie, DG;Jackson, EK
雌二醇抑制平滑肌细胞的生长；然而，涉及的机制尚不清楚。由于雌二醇刺激cAMP合成而腺苷抑制细胞生长，我们假设cAMP向腺苷的转化(即cAMP-腺苷途径)部分地介导了雌二醇对血管平滑肌细胞生长的抑制作用。为了验证这一假说，我们在1，3-二丙基-8-磺基苯基黄嘌呤(10nmol/L；A(1)/A(2)腺苷受体拮抗剂)、KF17837(10nmol/L；选择性A(2)腺苷受体拮抗剂)、8-环戊基-1，3-二丙基黄嘌呤(10nmol/L；选择性A(2)腺苷受体拮抗剂)和2‘，5’-脱氧腺苷(10mU/L；腺苷环化酶抑制剂)的存在和不存在的情况下，观察了雌二醇(0.001-1-1Mol/L)、8-环戊基-1，3-二丙基黄嘌呤(10nmol/L；选择性A(2)腺苷受体拮抗剂)和2‘，5’-脱氧腺苷(10mU/L；腺基环化酶抑制剂)对血清诱导的细胞DNA、胶原和总蛋白质合成及细胞数量的影响。雌二醇对细胞生长的所有指标均有抑制作用，其浓度依赖性抑制曲线右移(P
Estradiol inhibits smooth muscle cell growth; however, the mechanisms involved remain unclear. Because estradiol stimulates cAMP synthesis and adenosine inhibits cell growth, we hypothesized that the conversion of cAMP to adenosine (ie, the cAMP-adenosine pathway) mediates in part the inhibitory effects of estradiol on vascular smooth muscle cell growth. To test this hypothesis, we examined the effects of estradiol (0.001 to 1 mu mol/L) on serum-induced DNA, collagen, and total protein synthesis and cell number in the absence and presence of 1,3-dipropyl-8-psulfophenylxanthine (10 nmol/L; A(1)/A(2) adenosine receptor antagonist), KF17837 (10 nmol/L; selective A(2) adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (10 nmol/L; selective A(2) adenosine receptor antagonist), and 2',5'-dideoxyadenosine (10 mu mol/L; adenylyl cyclase inhibitor). Estradiol inhibited all measures of cell growth, and the concentration-dependent inhibitory curves for estradiol were shifted to the right (P