Liu Q S, Han S, Jia Y S, Ju G
Institute of Neurosciences, The Fourth Military Medical University, Xian 710032, People's Republic of China.
J Neurophysiol. 1999 Dec;82(6):3000-5. doi: 10.1152/jn.1999.82.6.3000.
Opioid peptides have profound inhibitory effects on the production of oxytocin and vasopressin, but their direct effects on magnocellular neuroendocrine neurons appear to be relatively weak. We tested whether a presynaptic mechanism is involved in this inhibition. The effects of mu-opioid receptor agonist D-Ala(2), N-CH(3)-Phe(4), Gly(5)-ol-enkephalin (DAGO) on excitatory and inhibitory transmission were studied in supraoptic nucleus (SON) neurons from rat hypothalamic slices using whole cell recording. DAGO reduced the amplitude of evoked glutamatergic excitatory postsynaptic currents (EPSCs) in a dose-dependent manner. In the presence of tetrodotoxin (TTX) to block spike activity, DAGO also reduced the frequency of spontaneous miniature EPSCs without altering their amplitude distribution, rising time, or decaying time constant. The above effects of DAGO were reversed by wash out, or by addition of opioid receptor antagonist naloxone or selective mu-antagonist Cys(2)-Tyr(3)-Orn(5)-Pen(7)-NH(2) (CTOP). In contrast, DAGO had no significant effect on the evoked and spontaneous miniature GABAergic inhibitory postsynaptic currents (IPSCs) in most SON neurons. A direct membrane hyperpolarization of SON neurons was not detected in the presence of DAGO. These results indicate that mu-opioid receptor activation selectively inhibits excitatory activity in SON neurons via a presynaptic mechanism.
阿片肽对催产素和血管加压素的产生具有深远的抑制作用，但其对大细胞神经内分泌神经元的直接作用似乎相对较弱。我们测试了这种抑制作用是否涉及突触前机制。使用全细胞记录法，研究了μ-阿片受体激动剂D-Ala(2)，N-CH(3)-Phe(4)，Gly(5)-ol-脑啡肽（DAGO）对大鼠下丘脑切片视上核（SON）神经元兴奋性和抑制性传递的影响。DAGO以剂量依赖性方式降低了诱发的谷氨酸能兴奋性突触后电流（EPSCs）的幅度。在存在河豚毒素（TTX）以阻断动作电位活动的情况下，DAGO还降低了自发微小EPSCs的频率，而不改变其幅度分布、上升时间或衰减时间常数。DAGO的上述作用可通过洗脱，或添加阿片受体拮抗剂纳洛酮或选择性μ-拮抗剂Cys(2)-Tyr(3)-Orn(5)-Pen(7)-NH(2)（CTOP）来逆转。相比之下，DAGO对大多数SON神经元中诱发的和自发的微小GABA能抑制性突触后电流（IPSCs）没有显著影响。在存在DAGO的情况下，未检测到SON神经元的直接膜超极化。这些结果表明，μ-阿片受体激活通过突触前机制选择性抑制SON神经元中的兴奋性活动。
