TOLBUTAMIDE EXCITES RAT GLUCORECEPTIVE VENTROMEDIAL HYPOTHALAMIC NEURONS BY INDIRECT INHIBITION OF ATP-K+ CHANNELS
TOLBUTAMIDE EXCITES RAT GLUCORECEPTIVE VENTROMEDIAL HYPOTHALAMIC NEURONS BY INDIRECT INHIBITION OF ATP-K+ CHANNELS
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DOI：
10.1111/j.1476-5381.1990.tb14116.x
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发表时间：
1990-11-01
影响因子：
7.3
通讯作者：
TREHERNE, JM
中科院分区：
文献类型：
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作者：
ASHFORD, MLJ;BODEN, PR;TREHERNE, JM
当应用于从大鼠培养的大脑皮层或新鲜分散的下丘脑腹内侧核（VMHN）神经元切除的由内而外的膜斑时，磺酰脲、甲苯磺丁脲（0.1 -10 mM）和格列本脲（0.1-100 μ M）显示不抑制ATP-K+通道电流。2大鼠大脑皮层和下丘脑膜中存在[3 H]-格列本脲的饱和结合位点，具有相似的亲和力常数。结合位点密度在下丘脑低于皮质。3获得了下丘脑脑片葡萄糖感受性VMHN神经元的细胞内记录。在没有葡萄糖的情况下，甲苯磺丁脲（0.1 mM）去极化这些细胞，增加膜电阻，并引起动作电位。4甲苯磺丁脲（0.1 mM）抑制葡萄糖感受性VMHN神经元细胞贴附记录的ATP-K+通道电流并诱导动作电流活性。5格列本脲（10-500 nM）本身对葡萄糖感受性VMHN神经元无影响，但可拮抗甲苯磺丁脲的作用。6结论是下丘脑（可能还有皮层）磺酰脲受体不直接与ATP-K+通道偶联。
1 The sulphonylureas, tolbutamide (0.1-10 mM) and glibenclamide (0.1-100 .mu.M) were shown not to inhibit ATP-K+ channel currents when applied to inside-out membrane patches excised from rat cultured cerebral cortex or freshly-dispersed ventromedial hypothalmic nucleus (VMHN) neurones. 2 Saturable binding sites for [3H]-glibenclamide, with similar affinity constants are present in rat cerebral cortex and hypothalamic membranes. The density of binding sites was lower in the hypothalamus than cortex. 3 Intracellular recordings from glucoreceptive VMHN neurones in hypothalamic slices were obtained. In the absence of glucose, tolbutamide (0.1 mM) depolarized these cells, increased membrane resistance and elicited action potentials. 4 Tolbutamide (0.1 mM) inhibited ATP-K+ channel currents and induced action current activity in cell-attached recordings from glucoreceptive VMHN neurones. 5 Glibenclamide (10-500 nM) had no effect per se on glucoreceptive VMHN neurones but did antagonize the actions of tolbutamide. 6 It is concluded that the hypothalamic (and perhaps cortical) sulphonylurea receptors are not directly coupled to ATP-K+ channels.