Modulation of the cough reflex by GABAA receptors in the caudal ventral respiratory group of the rabbit
Modulation of the cough reflex by GABAA receptors in the caudal ventral respiratory group of the rabbit
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DOI：
10.3389/fphys.2012.00403
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Mutolo, Donatella
中科院分区：
文献类型：
--
作者：
Cinelli, Elenia;Bongianni, Fulvia;Mutolo, Donatella
我们之前已经表明尾侧腹侧呼吸群（cVRG）是某些镇咳药物可能的作用部位，并且在确定咳嗽运动模式的呼气和吸气成分方面发挥着至关重要的作用。此外，据报道，cVRG 的髓质呼气神经元受到有效的 GABA 增益调节。本研究致力于研究 cVRG GABAA 受体在控制基线呼吸活动和对气管支气管树机械和化学（柠檬酸）刺激的咳嗽反应中的作用。为此目的，将荷包牡丹碱或蝇蕈醇双侧显微注射(30-50nl)到戊巴比妥钠麻醉、自主呼吸的兔子的cVRG中。由于 TE 降低，荷包牡丹碱 (1 mM) 增加了腹部活动峰值和呼吸频率。咳嗽反应增强主要是由于咳嗽次数的增加。 2小时内观察到恢复情况。相反，蝇蕈醇 (0.3 mM) 由于 TE 增加而消除了腹部活动并降低了呼吸频率。此外，咳嗽反应逐渐减少，并在 20 分钟内完全抑制。在相同位置显微注射荷包牡丹碱后 3 小时或 5 分钟内，咳嗽反应部分恢复。荷包牡丹碱和蝇蕈醇微量注射后，由鼻粘膜机械刺激引起的喷嚏反射持续存在。然而，荷包牡丹碱可增强呼气推力的次数和强度，而蝇蕈醇则可抑制呼气推力的次数和强度。结果证明，在 cVRG 水平上，GABAA 介导的有效抑制调节不仅对呼吸活动产生影响，而且对咳嗽和打喷嚏反射反应也产生影响。
We have previously shown that the caudal ventral respiratory group (cVRG) is a possible site of action of some antitussive drugs and plays a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. In addition, it has been reported that medullary expiratory neurons of the cVRG are subject to potent GABAergic gain modulation. This study was devoted to investigate the role of cVRG GABAA receptors in the control of baseline respiratory activity and cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. To this purpose, bilateral microinjections (30-50 nl) of bicuculline or muscimol were performed into the cVRG of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in TE. Cough responses were potentiated mainly owing to increases in the cough number. The recovery was observed within 2 h. On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in TE. In addition, cough responses were progressively reduced and completely suppressed within 20 min. Partial recovery of cough responses was achieved after 3 h or within 5 min following bicuculline microinjections at the same locations. The sneeze reflex induced by mechanical stimulation of the nasal mucosa persisted following bicuculline and muscimol microinjections. However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol. The results provide evidence that a potent GABAA-mediated inhibitory modulation is exerted at the level of the cVRG not only on respiratory activity, but also on cough and sneeze reflex responses.