Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.
Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.
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DOI：
10.1371/journal.pone.0008766
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发表时间：
2010-01-19
期刊：
影响因子：
3.7
通讯作者：
Greer JJ
中科院分区：
文献类型：
--
作者：
Lorier AR;Funk GD;Greer JJ
舌下运动神经元支配舌肌，对吸气时维持上呼吸道通畅至关重要。阿片类镇痛药抑制XII神经活动是一个重要的临床问题，但其潜在机制尚不清楚。目前还没有合适的药理学方法来对抗阿片类药物引起的XII神经活动的抑制，同时保持镇痛。Ampakines强化α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的反应。谷氨酸受体AMPA家族介导XII运动神经元的兴奋传递。因此，目的是确定μ-阿片受体激活对吸气活性的抑制作用是否包括对吸气前运动神经元对XII运动神经元突触的直接抑制作用，并确定其潜在机制。然后，我们检查了安帕平是否能对抗阿片类药物引起的XII运动神经元活性的抑制。使用新生大鼠髓质切片制备，在体外产生吸气相关输出。测量12根神经的吸气爆发幅度和频率。来自XII运动神经元的全细胞贴片记录被用来测量膜电流和突触事件。将μ-阿片受体激动剂DAMGO应用于XII核，通过突触前抑制兴奋性谷氨酸能传递来抑制吸气性XII运动神经元的输出。Ampakines （CX614和CX717）通过突触后作用于XII运动神经元，减轻damgo诱导的XII MN活性的抑制。阿片类镇痛药的吸气抑制作用包括突触前抑制XII运动神经元输出。安巴肽可拮抗μ-阿片受体介导的XII运动神经元吸入活性的抑制。这些结果表明，amppakines可能有助于对抗阿片类药物诱导的XII运动神经元活性抑制和由此导致的气道通畅损害。
Hypoglossal (XII) motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of μ-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s). We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity. A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the μ-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717) alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons. The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract μ-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.
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影响因子：
56.9
作者：
Gray, PA;Rekling, JC;Feldman, JL
通讯作者：
Feldman, JL
影响因子：
3.6
作者：
Arai, AC;Kessler, M;Lynch, G
通讯作者：
Lynch, G
DOI：
10.1016/0034-5687(86)90122-2
发表时间：
1986-06-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
BARTLETT, D;STJOHN, WM
通讯作者：
STJOHN, WM
DOI：
10.1164/rccm.200701-043up
发表时间：
2007-03-01
影响因子：
24.7
作者：
Horner, Richard L.;Bradley, T. Douglas
通讯作者：
Bradley, T. Douglas
DOI：
10.1046/j.1440-1681.2000.03192.x
发表时间：
2000-01-01
影响因子：
2.9
作者：
Bellingham, MC;Funk, GD
通讯作者：
Funk, GD