Contribution of central ¦Ì-receptors to switching pulmonary C-fibers-mediated rapid shallow breathing into an apnea by fentanyl in anesthetized rats

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• 作者：Zhenxiong Zhang ; Cancan Zhang ; Jianguo Zhuang ; Fadi Xu
• 关键词：Fentanyl ; Bronchopulmonary C-fiber ; The medial nucleus tractus solitarius ; The pre-Botzinger complex ; Respiratory rhythm
• 刊名：Brain Research
• 出版年：2012
• 出版时间：21 August, 2012
• 年：2012
• 卷：1469
• 期：Complete
• 页码：73-81
• 全文大小：731 K

文摘

Our previous study has shown that activating peripheral ¦Ì-receptors is necessary for switching the bronchopulmonary C-fibers (PCFs)-mediated rapid shallow breathing (RSB) into an apnea by systemic administration of fentanyl. The brainstem nuclei, such as the medial nucleus tractus solitarius (mNTS) and the pre-Botzinger complex (PBC), are required for completing the PCF-mediated respiratory reflexes. Moreover, these areas contain abundant ¦Ì-receptors and their activation prolongs expiratory duration (T_E). Thus, we asked if central ¦Ì-receptors, especially those in the mNTS and PBC, are involved in fully expressing this RSB-apnea switch by fentanyl. In anesthetized rats, the cardiorespiratory responses to right atrial injection of phenylbiguanide (PBG, 3-6 ¦Ìg/kg) were repeated after: (1) fentanyl (iv), a ¦Ì-receptor agonist, alone (8 ¦Ìg/kg, iv); (2) fentanyl following microinjection of naloxone methiodide (NXM, an opioid receptor antagonist) into the cisterna magna (10 ¦Ìg/4 ¦Ìl); (3) the bilateral mNTS (10 mM, 20 nl); or (4) PBC (10 mM, 20 nl). Our results showed that PBG shortened T_E by 37 ¡À 6 % (RSB, from 0.41 ¡À 0.05 to 0.26 ¡À 0.03 s, P < 0.01), but it markedly prolonged T_E by 5.8-fold (an apnea, from 0.50 ¡À 0.04 s to 2.9 ¡À 0.57 s, P < 0.01) after fentanyl (iv). Pretreatment with NXM injected into the cisterna magna or the PBC, but not the mNTS, prevented the fentanyl-induced switch. This study, along with our previous results mentioned above, suggests that although peripheral ¦Ì-receptors are essential for triggering the fentanyl-induced switch, central ¦Ì-receptors, especially those in the PBC, are required to fully exhibit such switch.

Summary statement: Our results suggest that the activation of central ¦Ì-receptors, especially those in the pre-Botzinger complex, is required for switching the pulmonary C-fiber-mediated rapid shallow breathing into an apnea by systemic administration of fentanyl.