Adenosine receptor‐mediated changes in cyclic AMP production and DNA synthesis in cultured arterial smooth muscle cells
Adenosine receptor‐mediated changes in cyclic AMP production and DNA synthesis in cultured arterial smooth muscle cells
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培养的动脉平滑肌细胞中腺苷受体介导的环 AMP 产生和 DNA 合成的变化
DOI：
10.1002/jcp.1041240314
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发表时间：
1985
影响因子：
5.6
通讯作者：
J. Nilsson
中科院分区：
文献类型：
--
作者：
B. Jonzon;B. Fredholm;J. Nilsson
研究了腺苷及其类似物L-苯基异丙基腺苷（L-PIA）和5′-N-乙基甲酰氨基腺苷（NECA）对大鼠动脉平滑肌细胞（SMC）生长停滞培养物中cAMP生成和血小板衍生生长因子（PDGF）刺激的DNA合成起始的影响。细胞内cAMP浓度通过微摩尔浓度的腺苷及其类似物剂量依赖性地增强，效力顺序为NECA >腺苷> L-PIA。腺苷受体拮抗剂8-苯基茶碱（8-PT）以竞争性方式拮抗该作用。腺苷的刺激作用可通过3 μM双嘧达莫（一种腺苷摄取阻断剂）增强。DNA合成以平行的方式被抑制，显示出相同的效力顺序。抑制作用可被8-PT拮抗。Forskolin是一种能够刺激腺苷酸环化酶催化单位从而形成cAMP的二萜，可增强微摩尔浓度的NECA和L-PIA的作用。毛喉素本身刺激cAMP产生并抑制DNA合成。在纳摩尔浓度下，L-PIA可抑制毛喉素刺激的cAMP增加。当用次优浓度的PDGF刺激起始时，纳摩尔浓度范围内的L-PIA也刺激DNA合成。这些发现表明SM上存在A1-和A2-亚型的腺苷受体，介导cAMP和DNA合成的双向变化。
The effects of adenosine and two analogs, L‐phenylisopropyladenosine (L‐PIA) and 5′‐N‐ethylcarboxamidoadenosine (NECA), on cAMP production and on platelet‐derived growth factor (PDGF)‐stimulated initiation of DNA synthesis in growth‐arrested cultures of rat arterial smooth muscle cells (SMC) were studied. The intracellular cAMP concentration was dose‐dependently enhanced by micromolar concentrations of adenosine and its analogs, with the potency order NECA > adenosine > L‐PIA. The effect was antagonized, in a competitive manner, by the adenosine receptor antagonist 8‐phenyltheophylline (8‐PT). The stimulatory effect of adenosine was enhanced by 3 μM dipyridamole an adenosine‐uptake blocker. DNA synthesis was inhibited in a parallel manner, showing the same potency order. The inhibition was antagonized by 8‐PT. Forskolin, a diterpene with the ability to stimulate the catalytic unit of adenylate cyclase and thereby cAMP formation, potentiated the effects of micromolar concentrations of NECA and L‐PIA. Forskolin, by itself, stimulated cAMP production and inhibited DNA synthesis. The forskolin‐stimulated increase in cAMP was inhibited by L‐PIA at nanomolr concentrations. L‐PIA in the nanomolar concentration range also stimulated DNA synthesis when initiation was stimulated with suboptimal concentrations of PDGF. These findings suggest the presence of adenosine receptors of both the A1‐ and A2‐subtype on SM‐mediating bidirectional changes of cAMP and DNA synthesis.