Tramadol produces outward currents by activating μ-opioid receptors in adult rat substantia gelatinosa neurones
Tramadol produces outward currents by activating μ-opioid receptors in adult rat substantia gelatinosa neurones
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DOI：
10.1038/sj.bjp.0706225
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发表时间：
2005-07-01
影响因子：
7.3
通讯作者：
Kumamoto, E
中科院分区：
文献类型：
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作者：
Koga, A;Fujita, T;Kumamoto, E
用全细胞膜片钳技术研究了曲马多代谢物单-二甲基曲马多（M1）对成年大鼠脊髓切片明胶质（SG）神经元的作用在所检测的41%的神经元中，超注入M1产生了-70毫伏的外向电流；这个反应在接近K+的平衡势时发生逆转。M1电流在冲洗后几乎没有下降，并持续了430 min在同一神经元中，M1电流的振幅与μ -阿片受体激动剂DAMGO产生的电流相关，且在μ -阿片受体拮抗剂CTAP而α - 2-肾上腺素受体拮抗剂育亨宾存在时，M1电流的振幅大幅降低。在M1对保持电流不起作用的神经元中，去甲肾上腺素产生了-70毫伏的外向电流与DAMGO反应相比，M1反应的振幅显示出300 μ M.5的EC50值。我们得出结论，M1通过激活成年大鼠SG神经元中的mu-阿片受体产生持续的超极化。这至少有助于曲马多减轻疼痛。
1 An action of a tramadol metabolite, mono-O-dimethyl-tramadol (M1), on substantia gelatinosa (SG) neurones in adult rat spinal cord slices was examined by using the whole- cell patch- clamp technique.2 In 41% of the neurones examined, superfusing M1 produced an outward current at -70 mV; this response reversed at a potential close to the equilibrium potential for K+. M1 current hardly declined and persisted for 430 min after its washout.3 M1 current correlated in amplitude with current produced by mu-opioid receptor agonist DAMGO in the same neurone, and largely reduced in amplitude in the presence of mu-opioid receptor antagonist CTAP but not alpha 2-adrenoceptor antagonist yohimbine. In a neurone where M1 had no effect on holding currents, noradrenaline produced an outward current at -70 mV.4 The amplitude of the M1 response, relative to that of the DAMGO response, exhibited an EC50 value of 300 mu M.5 We conclude that M1 produces a persistent hyperpolarization by activating mu-opioid receptors in adult rat SG neurones. This could contribute to at least a part of pain alleviation produced by tramadol.