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哮喘中β-2肾上腺素能受体功能障碍及多态性

Author
Ian P Hall, MD
Section Editors
Peter J Barnes, DM, DSc, FRCP, FRS
Benjamin A Raby, MD, MPH
Deputy Editor
Helen Hollingsworth, MD
Translators
王凌伟, 主任医师

引言

虽然多年以前人们就已认识到β肾上腺素能受体激动剂的强效支气管扩张作用，但直到20世纪80年代末，人们才开始理解其在β-2肾上腺素能受体作用的分子基础。该受体信号转导的机制以及β-2肾上腺素能受体功能障碍在哮喘发病机制中的潜在作用及其对治疗的反应总结在此。β受体激动剂治疗哮喘的临床应用将单独讨论。 (参见“β受体激动剂用于哮喘：急性给药及预防性应用”和“关于在治疗哮喘时长期使用β受体激动剂的争议”)

正常的受体调节

编码β-2肾上腺素能受体的基因位于染色体5q31[1]。其编码的蛋白质为G-蛋白偶联七跨膜域受体大家族的一员。该受体在肺内多种细胞中表达，包括气道平滑肌细胞和上皮细胞、血管内皮细胞和血管平滑肌细胞，以及炎症细胞，如肥大细胞、嗜酸性粒细胞和淋巴细胞。

刺激β-2受体会激活相关的G-蛋白(Gs)，Gs解离后释放出蛋白质亚基，即游离Gs-α。Gs-α激活腺苷酸环化酶，进而提高细胞内环磷酸腺苷(cyclic adenosine monophosphate, cAMP)水平。β-2肾上腺素能受体刺激的大多数细胞内作用都源于cAMP升高及由此引发的蛋白激酶A(protein kinase A, PKA)激活；还可能存在Gs-α对钙激活钾通道的直接非cAMP依赖性作用[2,3]。 (参见“肽类激素信号转导和调控”，关于‘G蛋白’一节)

β-2肾上腺素能受体的表达及其与细胞内信号通路的耦合受动态调节，提供了一个负反馈回路，可减少激动剂长期占据受体引起的细胞反应。受到激动剂刺激后，通过PKA依赖性通路或激活β-肾上腺素能受体激酶(beta-adrenergic receptor kinase, β-ARK，G蛋白受体激酶家族的一员)使受体磷酸化，从而减少与细胞内信号通路耦合。可能是由于不同种类细胞中β-ARK和/或PKA的数量及活性不同，延长激动剂刺激时，不同组织的退耦合程度并不相同。

受体的数量也受主动调节。

          

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Literature review current through: 2017-07 . | This topic last updated: 2017-04-27.
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