Beta2-agonist and anticholinergic drugs in the treatment of lung disease.

Beta2-agonist and anticholinergic drugs in the treatment of lung disease.
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β2 激动剂和抗胆碱能药物治疗肺部疾病。

DOI:
10.1513/pats.200504-038sr
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发表时间:
2005
期刊:
Proceedings of the American Thoracic Society
影响因子:
--
通讯作者:
A. Fryer
A. Fryer
中科院分区:
--
文献类型:
--
作者:
B. Proskocil;A. Fryer

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肺受交感神经系统和副交感神经系统的神经支配,其分别需要肾上腺素能受体和毒蕈碱受体的激活。肾上腺素能受体和毒蕈碱受体都是G蛋白偶联受体,它们共享许多相似的信号转导分子。这些受体在肺中广泛表达,并且特异性受体表达可在物种之间变化。受体表达的部位和亚型在正常气道功能的调节中起重要作用。从副交感神经纤维释放的乙酰胆碱激活位于气道平滑肌上的M3毒蕈碱受体,引起支气管收缩。为了对抗这种活性,位于副交感神经上的M2毒蕈碱受体抑制乙酰胆碱的释放。β 2-肾上腺素能受体在气道平滑肌上表达,其中激活引起支气管扩张。肾上腺素能受体也在自主神经上,在那里它们可以调节神经递质的释放。这些G蛋白偶联受体和下游通路之间的串扰确保了正常的气道功能。连接前和连接后的毒蕈碱和肾上腺素能受体控制自主神经张力,并且受体的任何不平衡或选择性阻断都可能损害系统并导致气道变得过度反应。在设计、开发和使用对抗气道疾病的药物时,必须考虑肾上腺素能受体和毒蕈碱受体的位置、功能和串扰。
The lungs are innervated by both the sympathetic and parasympathetic nervous systems, which entails the activation of adrenergic and muscarinic receptors, respectively. Both the adrenergic and muscarinic receptors are G-protein-coupled receptors, and they share many similar signal transduction molecules. These receptors are widely expressed in the lung and the specific receptor expression can vary among the species. The location and the subtype of receptor expressed are important in the regulation of normal airway function. Acetylcholine released from the parasympathetic fibers activates the M3 muscarinic receptors located on the airway smooth muscle, causing bronchoconstriction. To counter this activity, M2 muscarinic receptors located on the parasympathetic nerves inhibit release of acetylcholine. Beta2-adrenergic receptors are expressed on the airway smooth muscle where activation causes bronchodilation. Adrenergic receptors are also on the autonomic nerves where they can modulate neurotransmitter release. The crosstalk between these G-protein-coupled receptors and downstream pathways ensures normal airway function. The prejunctional and postjunctional muscarinic and adrenergic receptors control autonomic tone and any imbalance or selective blockade of the receptors can compromise the system and cause the airways to become hyperreactive. The location, function, and crosstalk of the adrenergic and muscarinic receptors must be considered in the design, development, and use of drugs to combat airway diseases.
DOI: 10.1152/ajplung.00255.2003
发表时间: 2004-02
期刊: American journal of physiology. Lung cellular and molecular physiology
影响因子: --
作者:
J. K. Walker;R. Gainetdinov;D. S. Feldman;P. McFawn;M. Caron;R. Lefkowitz;R. T. Premont;J. Fisher
通讯作者: J. K. Walker;R. Gainetdinov;D. S. Feldman;P. McFawn;M. Caron;R. Lefkowitz;R. T. Premont;J. Fisher
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发表时间: 1987
期刊: The American review of respiratory disease
影响因子: --
作者:
Gatto,C;Green,TP;Johnson,MG;Marchessault,RP;Seybold,V;Johnson,DE
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DOI: 10.1152/ajplung.1996.270.4.l630
发表时间: 1996
期刊: The American journal of physiology
影响因子: --
作者:
Myers,AC;Undem,BJ
通讯作者: Undem,BJ
DOI: 10.1172/jci116331
发表时间: 1993-04-01
影响因子: 15.9
作者:
JACOBY, DB;GLEICH, GJ;FRYER, AD
通讯作者: FRYER, AD
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DOI: 10.1016/0034-5687(96)00062-x
发表时间: 1996
期刊: Respiration physiology
影响因子: --
作者:
Zhang,XY;Zhu,FX;Robinson,NE
通讯作者: Robinson,NE