Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit
Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit
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DOI：
10.1152/ajpregu.00184.2008
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发表时间：
2008-07-01
影响因子：
2.8
通讯作者：
Pantaleo, Tito
中科院分区：
文献类型：
--
作者：
Mutolo, Donatella;Bongianni, Fulvia;Pantaleo, Tito
我们之前已经表明，孤立束核（NTS）尾部部分的嗜离子性谷氨酸受体，特别是在联合NTS中，在气管支气管咳嗽的调解中起着重要作用，P物质增强了这种反射。这个NTS区域可能是一些中枢作用的止咳药的作用部位，也是咳嗽药物敏感门控机制的一个组成部分。为了解决这些问题，我们研究了在戊巴比酮麻醉的自发呼吸家兔的尾侧NTS中微注射（30-50 nl）中枢作用止咳药物后，气管支气管机械刺激对基线呼吸活动和咳嗽反应的变化。[D-Ala(2), N-Me- Phe(4), Gly(5)-ol]-脑啡肽（DAMGO）和巴氯芬降低了基线呼吸频率，因为只有在较高浓度（分别为5 mM和1 mM）时，吸气时间才会增加。DAMGO （0.5 mM）和巴氯芬（0.1 mM）显著降低咳嗽次数、腹部活动峰值、气管压力峰值，并增加咳嗽相关的总周期持续时间。在较高浓度下，这些药物抑制咳嗽反射。这两种药物的作用被特异性拮抗剂（分别为10 mM纳洛酮和25 mM CGP-35348）所抵消。神经激肽-1 （NK1）受体拮抗剂CP-99,994 （10 mM）消除了咳嗽反应，而NK2受体拮抗剂MEN 10376 （5 mM）没有影响。结果表明，尾侧NTS是一些中枢作用药物的作用部位，并且可能是参与咳嗽调节的神经系统的组成部分。P物质释放在反射性咳嗽的调解中也起着重要作用。
We have previously shown that ionotropic glutamate receptors in the caudal portion of the nucleus tractus solitarii ( NTS), especially in the commissural NTS, play a prominent role in the mediation of tracheobronchial cough and that substance P potentiates this reflex. This NTS region could be a site of action of some centrally acting antitussive agents and a component of a drug-sensitive gating mechanism of cough. To address these issues, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30-50 nl) of centrally acting antitussive drugs into the caudal NTS of pentobarbitone-anesthetized, spontaneously breathing rabbits. [D-Ala(2), N-Me- Phe(4), Gly(5)-ol]-enkephalin ( DAMGO) and baclofen decreased baseline respiratory frequency because of increases in the inspiratory time only at the higher concentration employed ( 5 mM and 1 mM, respectively). DAMGO ( 0.5 mM) and baclofen ( 0.1 mM) significantly decreased cough number, peak abdominal activity, peak tracheal pressure, and increased cough-related total cycle duration. At the higher concentrations, these agents suppressed the cough reflex. The effects of these two drugs were counteracted by specific antagonists ( 10 mM naloxone and 25 mM CGP-35348, respectively). The neurokinin-1 (NK1) receptor antagonist CP-99,994 ( 10 mM) abolished cough responses, whereas the NK2 receptor antagonist MEN 10376 ( 5 mM) had no effect. The results indicate that the caudal NTS is a site of action of some centrally acting drugs and a likely component of a neural system involved in cough regulation. A crucial role of substance P release in the mediation of reflex cough is also suggested.