Systemic ovalbumin sensitization downregulates norepinephrine uptake by rabbit aortic smooth muscle cells.

Systemic ovalbumin sensitization downregulates norepinephrine uptake by rabbit aortic smooth muscle cells.
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全身卵清蛋白致敏下调兔主动脉平滑肌细胞去甲肾上腺素的摄取。

DOI:
10.1165/rcmb.2002-0030oc
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发表时间:
2002
影响因子:
6.4
通讯作者:
Wanner,Adam
Wanner,Adam
中科院分区:
医学1区
文献类型:
--
作者:
Horvath,Gabor;Torbati,Aliza;Conner,GregoryE;Salathe,Matthias;Wanner,Adam

文献摘要

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α-肾上腺素能受体上的去甲肾上腺素(NE)浓度部分受类固醇敏感性神经元儿茶酚胺摄取(摄取-2)调节。由于哮喘个体中α1-肾上腺素能激动剂和糖皮质激素(GS)诱导的支气管血管收缩增强,特应性可能与血管平滑肌细胞(SMC)摄取-2减少有关。因此,我们评估是否NE摄取和其特定的转运信使RNA(mRNA)的减少,在兔主动脉平滑肌细胞全身致敏卵清蛋白(OVA)。使用半定量荧光显微镜法测量NE摄取。皮质酮和O-甲基-异丙肾上腺素共孵育(各1 μM)20 min可降低SMC对NE的摄取,这是一种神经元单胺转运蛋白(EMT)抑制剂。OVA致敏兔NE摄取率比对照组低25.9±4.5%(平均值±SEM)(P< 0.05)。致敏血清对幼稚SMC摄取NE无影响。采用多重逆转录-聚合酶链反应检测主动脉平滑肌EMT mRNA表达。OVA致敏兔的表达较对照组低61.1±16.4%(P< 0.05)。这些数据表明,NE摄取的主动脉平滑肌细胞在特应性兔受损,并与降低转运蛋白mRNA的表达。哮喘患者的支气管动脉也可能存在同样的机制。
Norepinephrine (NE) concentration at α-adrenergic receptors is partially regulated by steroid-sensitive, extraneuronal catecholamine uptake (uptake-2). Because α1-adrenergic agonist– and glucocorticosteroid (GS)-induced bronchial vasoconstriction is enhanced in individuals with asthma, atopy could be associated with decreased uptake-2 by vascular smooth muscle cells (SMCs). We therefore evaluated whether NE uptake and its specific transporter messenger RNA (mRNA) were reduced in aortic SMCs of rabbits systemically sensitized with ovalbumin (OVA). NE uptake was measured using a semiquantitative fluorescence microscopic method. Corticosterone and O-methyl-isoprenaline, but not desipramine, co-incubation (1 μM each) for 20 min decreased NE uptake into SMCs, an inhibitor profile indicative of extraneuronal monoamine transporter (EMT). In OVA-sensitized rabbits, NE uptake was 25.9±4.5% (mean±SEM) lower than in control animals (P< 0.05). Sensitized serum had no effect on NE uptake into naive SMCs. EMT mRNA expression was measured in aortic smooth muscle, using multiplex reverse transcriptase-polymerase chain reaction. In OVA-sensitized rabbits, expression was 61.1±16.4% lower than in control animals (P< 0.05). These data demonstrate that NE uptake by aortic SMCs is impaired in atopic rabbits, and associated with a decreased transporter mRNA expression. The same mechanism may operate in bronchial arteries in individuals with asthma.