Release of ATP and glutamate in the nucleus tractus solitarii mediate pulmonary stretch receptor (Breuer-Hering) reflex pathway
Release of ATP and glutamate in the nucleus tractus solitarii mediate pulmonary stretch receptor (Breuer-Hering) reflex pathway
复制标题
DOI：
10.1113/jphysiol.2008.154567
复制
发表时间：
2008-08-15
影响因子：
5.5
通讯作者：
Spyer, K. Michael
中科院分区：
文献类型：
--
作者：
Gourine, Alexander V.;Dale, Nicholas;Spyer, K. Michael
Breuer-Hering充气反射是通过激活慢适应肺牵张受体传入（SAR）而启动的，所述SAR单突触地激活孤束背髓核（NTS）中的二级中继神经元。在这里，我们证明，在肺膨胀SAR释放ATP和谷氨酸从他们的中央终端激活这些NTS神经元。在麻醉和人工通气的大鼠，ATP和谷氨酸选择性微电极生物传感器放置在NTS检测到两个发射器相位锁定到肺膨胀的节奏释放。这种释放的ATP和谷氨酸是独立的中枢产生的呼吸节律，可以可逆地取消在迷走神经的传入传递的阻滞过程中，局部应用局部麻醉剂。微离子电泳应用ATP增加了所有测试的NTS二级中继神经元的活性，这些神经元从SAR接收单突触输入。单侧微量注射ATP到NTS网站，肺牵张受体传入终止产生中枢性呼吸暂停，模仿肺膨胀的影响。应用P2和谷氨酸受体拮抗剂（吡哆醛-5 '-磷酸-6-偶氮苯基-2'，4 '-二磺酸、苏拉明和犬尿烯酸）显著降低了基线肺膨胀诱导的二级中继神经元放电。这些数据表明，ATP和谷氨酸在NTS中从肺牵张受体传入的中央末梢释放，激活二级中继神经元，从而介导关键的呼吸反射-Breuer-Hering充气反射。
The Breuer-Hering inflation reflex is initiated by activation of the slowly adapting pulmonary stretch receptor afferents (SARs), which monosynaptically activate second-order relay neurones in the dorsal medullary nucleus of the solitary tract (NTS). Here we demonstrate that during lung inflation SARs release both ATP and glutamate from their central terminals to activate these NTS neurones. In anaesthetized and artificially ventilated rats, ATP- and glutamate-selective microelectrode biosensors placed in the NTS detected rhythmic release of both transmitters phase-locked to lung inflation. This release of ATP and glutamate was independent of the centrally generated respiratory rhythm and could be reversibly abolished during the blockade of the afferent transmission in the vagus nerve by topical application of local anaesthetic. Microionophoretic application of ATP increased the activity of all tested NTS second-order relay neurones which receive monosynaptic inputs from the SARs. Unilateral microinjection of ATP into the NTS site where pulmonary stretch receptor afferents terminate produced central apnoea, mimicking the effect of lung inflation. Application of P2 and glutamate receptor antagonists (pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid, suramin and kynurenic acid) significantly decreased baseline lung inflation-induced firing of the second-order relay neurones. These data demonstrate that ATP and glutamate are released in the NTS from the central terminals of the lung stretch receptor afferents, activate the second-order relay neurones and hence mediate the key respiratory reflex - the Breuer-Hering inflation reflex.