Theophylline-induced recovery in a hemidiaphragm paralyzed by hemisection in rats - Contribution of adenosine receptors
Theophylline-induced recovery in a hemidiaphragm paralyzed by hemisection in rats - Contribution of adenosine receptors
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DOI：
10.1016/s0028-3908(97)00190-1
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发表时间：
1998-01-01
影响因子：
4.7
通讯作者：
Goshgarian, HG
中科院分区：
文献类型：
--
作者：
Nantwi, KD;Goshgarian, HG
以前，我们证明了单次静脉注射茶碱可以诱导颈（C2）脊髓半切瘫痪的半侧膈肌恢复长达3小时。本研究比较了恩普罗林和茶碱对颈脊髓半切后半侧膈肌恢复的作用。这两种药物都是甲基黄嘌呤;然而，茶碱是腺苷受体拮抗剂，而恩普罗茶碱不是。为了进一步测试腺苷受体的参与，将腺苷的类似物N6（L-2-苯基异丙基）腺苷（L-PIA）与茶碱结合使用。在左侧C2脊髓半切后，动物单独或联合注射恩普罗茶碱（2.5-20 mg/kg）或茶碱（15 mg/kg）。茶碱注射的动物表现出强大的痉挛相关的活动，在以前静止的左膈神经和膈肌。在所有注射恩普罗茶碱的大鼠中均未观察到恢复。当恩普罗茶碱注射后，茶碱，恢复发生。先前L-PIA给药阻断茶碱诱导的恢复。当在茶碱后给药时，L-PIA减弱并随后阻断脊髓半切同侧的神经和半膈的诱导活动。我们的结论是，腺苷受体拮抗剂是牵连在半横膈半切后的恢复和茶碱可能是有用的治疗脊髓损伤患者的呼吸功能障碍。(C)1998爱思唯尔科技有限公司版权所有。
Previously, we demonstrated that a single intravenous injection of theophylline can induce recovery in a hemidiaphragm paralyzed by cervical (C2) spinal cord hemisection for up to 3 h. The present study contrasts the actions of enprofylline and theophylline on inducing hemidiaphragmatic recovery after cervical spinal cord hemisection. Both drugs are methylxanthines; however, theophylline is an adenosine receptor antagonist while enprofylline is not. To further test the involvement of adenosine receptors, N6 (L-2-phenylisopropyl) adenosine (L-PIA), an analogue of adenosine was used in conjunction with theophylline. Following a left C2 spinal cord hemisection, animals were injected with either enprofylline (2.5-20 mg/kg) or theophylline (15 mg/kg) alone or in combination. Theophylline-injected animals demonstrated robust respiratory-related activity in the previously quiescent left phrenic nerve and hemidiaphragm. No recovery was observed in any of the enprofylline-injected rats. When enprofylline injection was followed later with theophylline, recovery occurred. Prior L-PIA administration blocked theophylline-induced recovery. When given after theophylline, L-PIA attenuated and then blocked the induced activity in both the nerve and hemidiaphragm ipsilateral to spinal cord hemisection. We conclude that adenosine receptor antagonism is implicated in hemidiaphragmatic recovery after hemisection and theophylline may be useful in the treatment of spinal cord injured patients with respiratory deficits. (C) 1998 Elsevier Science Ltd. All rights reserved.