Alpha 1-adrenergic receptor mRNA level is regulated by norepinephrine in rabbit aortic smooth muscle cells.
Alpha 1-adrenergic receptor mRNA level is regulated by norepinephrine in rabbit aortic smooth muscle cells.
复制标题
兔主动脉平滑肌细胞中的 α1-肾上腺素能受体 mRNA 水平受去甲肾上腺素调节。
DOI：
10.1073/pnas.87.16.6268
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发表时间：
1990
影响因子：
11.1
通讯作者：
Colucci,WS
中科院分区：
文献类型：
--
作者：
IzzoJr,NJ;Seidman,CE;Collins,S;Colucci,WS
长时间的激动剂暴露导致兔主动脉平滑肌细胞中α 1-肾上腺素能受体密度降低。α 1-肾上腺素能受体的cDNA用于评估去甲肾上腺素对来自兔主动脉的培养血管平滑肌细胞中α 1-肾上腺素能受体mRNA水平的影响。去甲肾上腺素引起α 1-肾上腺素能受体mRNA一过性降低（81% +/- 5%; n = 9）。该效应具有浓度依赖性（EC 50，约0.3 μ M;最大效应，10 μ M）。去甲肾上腺素暴露4小时后出现最大下降，随后逐渐恢复到对照水平，24 hr. The mRNA水平的下降被哌唑嗪阻断，但不是普萘洛尔，并模仿苯肾上腺素。这些结果表明，该效应是由α 1-肾上腺素能受体的刺激介导的，并表明它涉及一个或多个α 1-肾上腺素能偶联的第二信使途径。由去甲肾上腺素引起的α 1-肾上腺素能受体mRNA的减少超过由放线菌素D引起的减少，表明去甲肾上腺素可能引起α 1-肾上腺素能受体mRNA稳定性的降低。放线菌素D还阻断了去甲肾上腺素诱导的mRNA水平降低，进一步表明去甲肾上腺素的作用需要诱导转录，推测导致合成一种不稳定因子，这是去甲肾上腺素对α 1-肾上腺素能受体mRNA水平的作用所必需的。
Prolonged agonist exposure results in a decrease in the density of alpha 1-adrenergic receptors in rabbit aortic smooth muscle cells. A cDNA for the alpha 1-adrenergic receptor was used to assess the effect of norepinephrine on alpha 1-adrenergic receptor mRNA level in cultured vascular smooth muscle cells from the rabbit aorta. Norepinephrine caused a transient decrease (81% +/- 5%; n = 9) in alpha 1-adrenergic receptor mRNA. The effect was concentration dependent (EC50, approximately 0.3 microM; maximal effect, 10 microM). The maximum decrease occurred after 4 hr of exposure to norepinephrine and was followed by a gradual return to control levels by 24 hr. The decrease in mRNA level was blocked by prazosin, but not propranolol, and was mimicked by phenylephrine. These results indicate that the effect is mediated by stimulation of the alpha 1-adrenergic receptor and suggest that it involves one or more alpha 1-adrenergic-coupled second messenger pathways. The decrease in alpha 1-adrenergic receptor mRNA caused by norepinephrine exceeds that caused by actinomycin D, suggesting that norepinephrine may cause a decrease in the stability of alpha 1-adrenergic receptor mRNA. Actinomycin D also blocked the norepinephrine-induced decrease in mRNA level, further suggesting that the effect of norepinephrine requires induction of transcription, presumably leading to synthesis of a labile factor that is necessary for the effect of norepinephrine on alpha 1-adrenergic receptor mRNA level.