Changes in adenosine A(1)- and A(2)-receptor expression during adipose cell differentiation
Changes in adenosine A(1)- and A(2)-receptor expression during adipose cell differentiation
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DOI：
10.1016/0303-7207(95)03728-4
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发表时间：
1996-03-01
影响因子：
4.1
通讯作者：
Negrel, R
中科院分区：
文献类型：
--
作者：
Borglum, JD;Vassaux, G;Negrel, R
两种腺苷受体 A(1) 和 A(2) 与腺苷酸环化酶的刺激（A(2)）或抑制（A(1)）相关。使用克隆细胞系 Ob1771，我们研究了汇合后前 3 天暴露于地塞米松和 3-异丁基-1-甲基黄嘌呤 (IBMX) 加速的脂肪转化过程中两种受体的表达。还研究了两种受体介导的前脂肪细胞分化和脂肪细胞代谢的影响。两种腺苷激动剂NECA和PIA分别用作A(2)-和A(1)-受体的优先激动剂。在小鼠克隆系和人类原代培养物的前脂肪细胞（刚刚汇合）中，NECA 剂量依赖性地刺激 cAMP 产生，其效力显着高于 PIA（P < 0.01）。在脂肪细胞中（汇合后 16 天），NECA 对毛喉素刺激的 cAMP 产生产生双相作用，即 NECA 在飞摩尔至皮摩尔浓度范围内具有明显的抑制作用，而这种作用在较高浓度下逐渐减弱。然而，PIA 在汇合后 16 天的脂肪细胞中的作用纯粹是抑制 cAMP 产生（IC50：33.52 +/- 0.44 fM）和脂肪分解（64% +/- 7%；P < 0.01）。这些发现得到了 Northern blot 分析的证实，该分析显示 A(1)-受体 mRNA 只在成熟脂肪细胞中表达，而 A(2)-受体 mRNA 在分化过程中逐渐下降，除了汇合后 16 天的细胞外。此外，NECA 显着增强了皮质酮诱导分化的效果 46.8% (P < 0.05)，但无论是单独作用还是与卡前列环素 (cPGI(2)) 协同作用，均未产生任何脂肪形成功效。因此，内源性腺苷可能对分别通过刺激性 A(2) 和抑制性 A(1) 受体介导的脂肪组织代谢具有双峰作用，作为脂肪转化的函数。
Two adenosine receptors A(1) and A(2) are associated with either stimulation (A(2)) or inhibition (A(1)) of adenylate cyclase. Using the clonal cell line Ob1771, we have studied the expression of the two receptors during the process of adipose conversion accelerated by exposure to dexamethasone and 3-isobutyl-1-methylxanthine (IBMX) during the first 3 days post-confluence. The effects mediated by the two receptors on preadipocyte differentiation and adipocyte metabolism were also investigated. The two adenosine agonists NECA and PIA were used as preferential agonists of the A(2)- and A(1)-receptor, respectively. In preadipose cells (just confluent), both of the mouse clonal line and human primary culture, NECA dose-dependently stimulated cAMP production with a significant higher potency (P < 0.01) than did PIA. In adipose cells (16-day post-confluent) NECA was found to exert a biphasic effect on forskolin-stimulated cAMP production i.e., NECA was dearly inhibitory in the femto- to picomolar concentration range whereas this effect gradually diminished at higher concentrations. The effect of PIA in 16-day post-confluent adipose cells however, was purely inhibitory on both cAMP production (IC50: 33.52 +/- 0.44 fM) and lipolysis (64% +/- 7%; P < 0.01). These findings were corroborated by Northern blot analysis which revealed A(1)-receptor mRNA to be exclusively expressed in the mature adipocytes, whereas A(2)-receptor mRNA gradually declined during the differentiation process except in 16-day post-confluent cells. In addition, NECA significantly enhanced the effect of corticosterone-induced differentiation by 46.8% (P < 0.05) but failed to have any adipogenic potency acting either alone or in concert with carbaprostacyclin (cPGI(2)). Thus, endogenous adenosine may have a bimodal action on adipose tissue metabolism mediated through stimulatory A(2)- and inhibitory A(1)-receptors, respectively, as a function of adipose conversion.