Inenaga K, Nagatomo T, Nakao K, Yanaihara N, Yamashita H
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Neuroscience. 1994 Jan;58(2):331-40. doi: 10.1016/0306-4522(94)90039-6.
To investigate the effects of the endogenous kappa-receptor agonists dynorphin and leumorphin on neurons of the supraoptic nucleus in the rat hypothalamus, intracellular recordings were made from 62 supraoptic neurons in slice preparations. Bath application of dynorphin and leumorphin at 10(-7) M to 3 x 10(-6) M decreased the spontaneous firing rate with slight hyperpolarization of the membrane potential (-3.8 +/- 0.5 mV, mean +/- S.E.M.) but did not detectably change input resistance. The inhibitory effects were blocked by the relatively selective kappa-antagonist MR-2266. The synthetic kappa-receptor agonist U-50,488H had similar inhibitory effects on supraoptic neurons. Postsynaptic potentials evoked by electrical stimulation dorsal or dorsolateral to the supraoptic nucleus were suppressed by dynorphin and leumorphin. Morphine and [D-Ala, D-Leu]enkephalin, which are relatively selective to mu- and delta-receptors, respectively, influenced the postsynaptic potentials less. Dynorphin and leumorphin also decreased the duration of action potentials that were prolonged by either bath application of tetraethylammonium chloride at 5-10 mM or intracellular injection of Cs ions from the recording electrodes which were filled with 3 M cesium citrate. The prolongation was blocked by 1 mM MnCl2 and 2 mM CoCl2, which suggested that the components were due to voltage-dependent Ca2+ influx. The results suggest that endogenous kappa-receptor agonists inhibit neurosecretory cells of the supraoptic nucleus to suppress synaptic events and Ca2+ components of action potentials.
为研究内源性κ受体激动剂强啡肽和亮甲啡肽对大鼠下丘脑视上核神经元的影响，在脑片标本中对62个视上神经元进行了细胞内记录。浴槽中加入浓度为10⁻⁷ M至3×10⁻⁶ M的强啡肽和亮甲啡肽，可降低自发放电频率，同时膜电位出现轻微超极化（-3.8±0.5 mV，平均值±标准误），但未检测到输入电阻有明显变化。相对选择性的κ拮抗剂MR - 2266可阻断这种抑制作用。合成的κ受体激动剂U - 50,488H对视上神经元也有类似的抑制作用。视上核背侧或背外侧电刺激诱发的突触后电位受到强啡肽和亮甲啡肽的抑制。分别对μ受体和δ受体相对选择性的吗啡和[D - Ala，D - Leu]脑啡肽对突触后电位的影响较小。强啡肽和亮甲啡肽还可缩短动作电位的持续时间，动作电位的延长是通过在浴槽中加入5 - 10 mM的四乙铵氯化物或从充满3 M柠檬酸铯的记录电极内向细胞内注射铯离子诱导产生的。1 mM的氯化锰和2 mM的氯化钴可阻断这种延长，这表明其成分是由于电压依赖性钙内流所致。结果表明，内源性κ受体激动剂抑制视上核的神经分泌细胞，从而抑制突触活动和动作电位的钙成分。
