Responses to [D-Ala2, MePhe4, Gly-ol5]enkephalin, a selective agonist for mu-receptors, were recorded intracellularly from 26 neurons in slices of guinea-pig hypothalamus. Of eight cells tested in the supraoptic nucleus, all of which had electrical properties characteristic of magnocellular neuroendocrine cells, four were sensitive to the agonist applied in the perfusion bath or with microdrops. The main effect was a decrease or suppression of spontaneous firing. In the paraventricular nucleus, seven of 18 cells tested also had electrophysiological characteristics similar to magnocellular neurons: two of them were sensitive to the mu-agonist and the effect was similar to that observed in the supraoptic nucleus. The remaining paraventricular neurons displayed low-threshold Ca2+ spikes, and thus had electrophysiological characteristics different from putative magnocellular neurons. Ten of 11 cells with low-threshold Ca2+ spikes were hyperpolarized by more than 10 mV by the mu-agonist, and showed a 33 +/- 1.9% (S.E.M.) decrease in input resistance. In both types of cells, when synaptic transmission was blocked with tetrodotoxin, the mu-agonist could still induce a hyperpolarization, suggesting that the effect was in part direct. Hyperpolarization was also obtained when the Cl- reversal potential was shifted to more positive values by using KCl electrodes, thus excluding a Cl- conductance mechanism. These results provide evidence that opioid peptides can directly inhibit hypothalamic neurons, that the mechanism is an increase in K+ conductance, and that two types of hypothalamic neurons appear to have different sensitivities to a mu-agonist.

译文

:对豚鼠下丘脑切片中26个神经元的细胞内记录了对[D-Ala2,MePhe4,Gly-ol5]脑啡肽(一种针对mu受体的选择性激动剂)的反应。在视上核中测试的8个细胞中,所有细胞均具有大细胞神经内分泌细胞的电特性,其中4个对灌注浴或微滴中使用的激动剂敏感。主要作用是减少或抑制自发放电。在脑室旁核中,测试的18个细胞中有7个也具有类似于大细胞神经元的电生理特性:其中两个对mu激动剂敏感,作用类似于在视上核中观察到的。其余的脑室旁神经元显示低阈值的Ca2尖峰,因此具有与假定的大细胞神经元不同的电生理特性。 mu激动剂将11个具有低阈值Ca2尖峰的细胞中的10个超极化了10 mV以上,显示输入电阻降低了33 /-1.9%(S.E.M.)。在两种类型的细胞中,当突触传递被河豚毒素阻断时,mu-激动剂仍可诱导超极化,这表明这种作用部分是直接的。当通过使用KCl电极将Cl-反转电位移动到更正值时,也获得了超极化,因此排除了Cl-电导机制。这些结果提供证据表明阿片样物质肽可以直接抑制下丘脑神经元,其机制是钾电导增加,并且两种类型的下丘脑神经元似乎对μ-激动剂具有不同的敏感性。

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