Opioid receptors on bulbospinal respiratory neurons are not activated during neuronal depression by clinically relevant opioid concentrations.
Opioid receptors on bulbospinal respiratory neurons are not activated during neuronal depression by clinically relevant opioid concentrations.
复制标题
在神经元抑制期间，临床相关的阿片类药物浓度不会激活球脊髓呼吸神经元上的阿片类药物受体。
DOI：
10.1152/jn.90620.2008
复制
发表时间：
2008
影响因子：
2.5
通讯作者：
Stuth,EckehardA
中科院分区：
文献类型：
--
作者：
Stucke,AstridG;Zuperku,EdwardJ;Sanchez,Antonio;Tonkovic-Capin,Mislav;Tonkovic-Capin,Viseslav;Mustapic,Sanda;Stuth,EckehardA
阿片类药物抑制脑干神经元的活动，但临床浓度的机制是否包括直接的神经元效应或网络效应尚未解决。我们进行了细胞外记录的放电活动的单一呼吸神经元的尾侧腹侧呼吸组的去脑犬，这是前运动神经元的可能性为90%。我们使用多管玻璃微电极，它允许伴随的阿片受体激动剂或拮抗剂到神经元上的高度局部化的皮可喷射。μ受体激动剂[d-Ala 2，N-Me-Phe 4，gly-ol 5]-脑啡肽的皮可喷射（DAMGO，1 mM）降低峰值放电频率（平均值±标准差）为68 ± 22%（n= 12），δ 1激动剂-Pen 2，5-脑啡肽δ 2受体激动剂[d-Ala 2] deltorphin-II为86 ± 17%（1 mM，n= 15）。吸气神经元的相应值分别为：64 ± 12%（n= 11）、48 ± 30%（n= 12）和75 ± 15%（n= 11）。纳洛酮完全逆转了这些作用。吗啡（0.01-1 mM）的皮可喷射抑制大多数神经元的浓度依赖性的方式，最大63%（n= 27）。瑞芬太尼（240-480 nM）的皮可喷射没有引起任何显著的吸气（n= 11）或呼气神经元（n= 9）的抑制。4.静脉注射瑞芬太尼（0.2-0.6 μg·kg-1·min-1）使神经元峰放电频率降低至60 ± 12%（吸气，n= 7）和58 ± 11%（呼气，n= 11）。然而，纳洛酮的局部皮可喷射并不能逆转神经元的抑制。结果表明，犬呼吸前运动神经元上存在μ、δ1和δ 2受体。吗啡和瑞芬太尼的临床浓度没有引起局部抑郁。这种缺乏效果和局部纳洛酮无法逆转静脉注射瑞芬太尼引起的神经元抑制表明，临床浓度的阿片类药物对呼吸球脊髓前运动神经元上游机制产生抑制作用。
Opioids depress the activity of brain stem respiratory-related neurons, but it is not resolved whether the mechanism at clinical concentrations consists of direct neuronal effects or network effects. We performed extracellular recordings of discharge activity of single respiratory neurons in the caudal ventral respiratory group of decerebrate dogs, which were premotor neurons with a likelihood of 90%. We used multibarrel glass microelectrodes, which allowed concomitant highly localized picoejection of opioid receptor agonists or antagonists onto the neuron. Picoejection of the μ receptor agonist [d-Ala2, N-Me-phe4, gly-ol5]-enkephalin (DAMGO, 1 mM) decreased the peak discharge frequency (mean ± SD) of expiratory neurons to 68 ± 22% (n= 12), the δ1agonistd-Pen2,5-enkephalin (DPDPE, 1 mM) to 95 ± 11% (n= 15), and δ2receptor agonist [d-Ala2] deltorphin-II to 86 ± 17% (1 mM,n= 15). The corresponding values for inspiratory neurons were: 64 ± 12% (n= 11), 48 ± 30% (n= 12), and 75 ± 15% (n= 11), respectively. Naloxone fully reversed these effects. Picoejection of morphine (0.01–1 mM) depressed most neurons in a concentration dependent fashion to maximally 63% (n= 27). Picoejection of remifentanil (240–480 nM) did not cause any significant depression of inspiratory (n= 11) or expiratory neurons (n= 9). 4. Intravenous remifentanil (0.2–0.6 μg·kg−1·min−1) decreased neuronal peak discharge frequency to 60 ± 12% (inspiratory,n= 7) and 58 ± 11% (expiratory,n= 11). However, local picoejection of naloxone did not reverse the neuronal depression. Our data suggest that μ, δ1, and δ2receptors are present on canine respiratory premotor neurons. Clinical concentrations of morphine and remifentanil caused no local depression. This lack of effect and the inability of local naloxone to reverse the neuronal depression by intravenous remifentanil suggest that clinical concentrations of opioids produce their depressive effects on mechanisms upstream from respiratory bulbospinal premotor neurons.