INHIBITION OF BRONCHIAL HYPERRESPONSIVENESS BY THE GABA-AGONIST BACLOFEN
INHIBITION OF BRONCHIAL HYPERRESPONSIVENESS BY THE GABA-AGONIST BACLOFEN
复制标题
DOI：
10.1378/chest.106.3.758
复制
发表时间：
1994-09-01
期刊：
影响因子：
9.6
通讯作者：
ALMENOFF, PL
中科院分区：
文献类型：
--
作者：
DICPINIGAITIS, PV;SPUNGEN, AM;ALMENOFF, PL
γ -氨基丁酸（GABA）是一种众所周知的中枢神经系统的抑制性递质。近年来，GABA及其受体已被证实存在于外周组织，包括肺组织。-氨基丁酸和伽马氨基丁酸激动剂巴氯芬在动物研究中已被证明可抑制气道对各种支气管收缩剂的反应。这些研究结果提示巴氯芬在治疗人类气道高反应性方面的作用的可能性。我们最近发现，颈脊髓损伤（四肢瘫痪）患者对甲胆碱均表现出高反应性。颈椎横断后交感气道神经支配的中断和由此产生的无对抗胆碱能张力被认为可以解释这一现象。我们比较了另一组健康的四肢瘫痪非吸烟者（n=8）的支气管反应性（PC20）和维持巴氯芬缓解肌肉痉挛的相似组（n=6）。对照组的平均PC20 （mg/ml）为1.42+/-1.6(SD)，巴氯芬组为15.0+/-9.1 （p=0.001）。慢性巴氯芬治疗维持的颈脊髓损伤患者对支气管高反应性的抑制表明，该药物能够阻断气道内神经元乙酰胆碱的释放，并可能对气道平滑肌有直接作用。巴氯芬的这种作用，以及它在动物肺中抑制其他炎症介质释放的能力，支持了对这种药物作为哮喘治疗潜在治疗剂的进一步研究。
gamma-Aminobutyric acid (GABA) is a well-known inhibitory transmitter of the central nervous system. Recently, the presence of GABA and its receptors has been confirmed in peripheral tissues, including lung tissue. gamma-Aminobutyric acid and the GABA-agonist baclofen have been shown in animal studies to inhibit airway responsiveness to various bronchoconstricting agents. The results of these investigations suggest the possibility of a role for baclofen in the therapy of human airway hyperreactivity. We recently showed that subjects with cervical spinal cord injury (quadriplegia) uniformly exhibit hyperresponsiveness to methacholine. The interruption of sympathetic airway innervation and resultant unopposed cholinergic tone occurring after transection of the cervical spine are thought to explain this phenomenon. We compared bronchial responsiveness with methacholine (PC20) in a control group of otherwise healthy quadriplegic nonsmokers (n=8) with a similar group of subjects (n=6) maintained on baclofen for the relief of muscle spasm. Mean PC20 (mg/ml) among the control group was 1.42+/-1.6(SD) vs 15.0+/-9.1 in the baclofen group (p=0.001). The inhibition of bronchial hyperresponsiveness in subjects with cervical spinal cord injury maintained on chronic baclofen therapy suggests the drug's ability to block neuronal acetylcholine release within airways, as well as a possible direct effect on airway smooth muscle. This action of baclofen, along with its documented ability in animal lung to inhibit release of other inflammatory mediators, supports further investigation of this drug as a potential therapeutic agent for asthma treatment.