Wang R A, Randić M
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
Neurosci Lett. 1994 Oct 24;180(2):109-13. doi: 10.1016/0304-3940(94)90499-5.
Whole-cell voltage-clamp technique was used to examine the effects of a mu-opioid receptor agonist DAGO (Tyr-D-Ala-Gly-Me-Phe-Gly-ol-enkephalin) on GABA-induced currents in acutely isolated spinal dorsal horn (DH) neurons from laminae I-IV of young rats. We found that a bicuculline-sensitive GABA-induced current was potentiated by DAGO (0.5-500 nM), in a dose-dependent manner, in approximately 62% of the tested cells. The elevated GABA responses outlasted the period of DAGO application, and either recovered within 10 min after the removal of the peptide or persisted for up to 50 min. The potentiating effect of DAGO was reduced or prevented by naloxone and the mu-opioid receptor-selective antagonist beta-funaltrexamine. A similar enhancing effect on the membrane currents activated by administration of muscimol, a GABAA receptor-specific agonist, was produced by DAGO. In addition, a transient depression of GABA responses was observed in approximately 25% of the cells tested. These results indicate that the mu-opioid agonist DAGO modulates the sensitivity of postsynaptic GABAA receptors in a large proportion of spinal neurons from laminae I-IV, with the major effect being facilitation. The DAGO action could contribute to the regulation of the strength of primary afferent neurotransmission, including nociception.
采用全细胞膜片钳技术，研究μ阿片受体激动剂DAGO（酪氨酰-D-丙氨酰-甘氨酰-甲基苯丙氨酰-甘氨醇脑啡肽）对急性分离的幼年大鼠脊髓背角I-IV层神经元中γ-氨基丁酸（GABA）诱导电流的影响。我们发现，在大约62%的受试细胞中，DAGO（0.5 - 500 nM）以剂量依赖的方式增强了荷包牡丹碱敏感的GABA诱导电流。增强后的GABA反应持续时间超过DAGO作用时间，在去除该肽后10分钟内恢复，或者持续长达50分钟。纳洛酮和μ阿片受体选择性拮抗剂β-芬氟拉明可降低或阻断DAGO的增强作用。DAGO对给予GABAA受体特异性激动剂蝇蕈醇激活的膜电流也有类似的增强作用。此外，在大约25%的受试细胞中观察到GABA反应出现短暂抑制。这些结果表明，μ阿片受体激动剂DAGO在很大比例的脊髓背角I-IV层神经元中调节突触后GABAA受体的敏感性，主要作用是易化。DAGO的作用可能有助于调节初级传入神经传递的强度，包括伤害性感受。
