Inhibitory actions of delta 1-, delta 2-, and mu-opioid receptor agonists on excitatory transmission in lamina II neurons of adult rat spinal cord
Inhibitory actions of delta 1-, delta 2-, and mu-opioid receptor agonists on excitatory transmission in lamina II neurons of adult rat spinal cord
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DOI：
10.1523/jneurosci.14-08-04965.1994
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发表时间：
1994-08
期刊：
影响因子：
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通讯作者：
S. Glaum;R.J. Miller;DL Hammond
中科院分区：
文献类型：
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作者：
S. Glaum;R.J. Miller;DL Hammond
这项研究利用视觉识别的幼年大鼠腰髓横断薄片中的板层II神经元制成的全细胞记录，研究了选择性激活β1、β2或u阿片受体的电生理学后果。用荷包牡丹碱和士的宁阻断抑制性传入，用D-2-氨基-5-膦戊酸阻断NMDA受体，在同侧背根入区电诱发兴奋性突触后电流(EPSCs)或电位(EPSP)。沐浴Mu受体激动剂[D-Ala2，N-MePhe4，Gly5-ol]脑啡肽(DAMGO)或Delta1受体激动剂[D-Pen2，D-Pen5]脑啡肽(DPDPE)可使诱发的EPSP/EPSC的幅度呈线性、浓度依赖性降低。相比之下，Delta2受体激动剂[D-Ala2，Glu4]Deltorphin(DELT)在100微米时不能使诱发的EPSP/EPSC减少50%以上，这是所测试的最高浓度。在使诱发的EPSP/EPSCs减少40-60%的浓度下，DAMGO、DPDPE和DELT都不能降低短暂压力喷射(S)-α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸所产生的突触后电流的幅度，提示这些阿片受体激动剂存在突触前作用部位。应用Delta2受体拮抗剂200 nM纳曲本(NTB)使DELT的EC75竞争性增加15.3倍，但对DPDPE和DAMGO均无拮抗作用。在1微米NTB存在下，DELT的EC75值进一步增加了169.7倍。然而，这种高浓度的NTB也以非竞争性的方式使DPDPE的EC50增加约三倍，并以非竞争性的方式拮抗DAMGO。
This study examined the electrophysiological consequences of selective activation of delta 1-, delta 2-, or mu-opioid receptors using whole- cell recordings made from visually identified lamina II neurons in thin transverse slices of young adult rat lumbar spinal cord. Excitatory postsynaptic currents (EPSCs) or potentials (EPSPs) were evoked electrically at the ipsilateral dorsal root entry zone after blocking inhibitory inputs with bicuculline and strychnine, and NMDA receptors with D-2-amino-5-phosphonopentanoic acid. Bath application of the mu receptor agonist [D-Ala2, N-MePhe4, Gly5-ol]enkephalin (DAMGO) or the delta 1 receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) produced a long-linear, concentration-dependent reduction in the amplitude of the evoked EPSP/EPSC. By comparison, the delta 2 receptor agonist [D- Ala2,Glu4]deltorphin (DELT) was unable to reduce the evoked EPSP/EPSC by more than 50% at 100 microM, the highest concentration tested. At concentrations that reduced evoked EPSP/EPSCs by 40–60%, neither DAMGO, DPDPE, nor DELT decreased the amplitude of the postsynaptic current produced by brief pressure ejection of (S)-alpha-amino-3-hydroxy-5- methyl-4-isoxazole-propionic acid, suggesting a presynaptic site of action of these opioid receptor agonists. Bath application of 200 nM naltriben (NTB), a delta 2 receptor antagonist, competitively increased the EC75 of DELT by 15.3-fold, but did not antagonize either DPDPE or DAMGO. The EC75 of DELT was further increased by 169.7-fold in the presence of 1 microM NTB. However, this high concentration of NTB also increased the EC50 of DPDPE by about threefold in a noncompetitive manner and antagonized DAMGO in a noncompetitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)