Sutoo D, Akiyama K, Iimura K
Pharmacol Biochem Behav. 1985 Oct;23(4):627-31. doi: 10.1016/0091-3057(85)90428-9.
This investigation was carried out to determine if calcium prolongation of ethanol-induced sleep is mediated by calmodulin and a calmodulin-dependent protein kinase. The duration of ethanol-induced sleeping time in ddY male mice was measured following the administration of CaCl2 (20, 40, 80 and 200 mumol/kg, intraperitoneally (IP) both with and without the calmodulin antagonists, W-7: [N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide] (4.2 micrograms/mouse, intraventricular (IVT) or trifluoperazine (TFP; 1.8 micrograms/mouse, IVT). When CaCl2 was administered in a dose dependent manner the duration of ethanol-induced sleep was prolonged. The prolongation was antagonized by W-7 and TFP. When mice were treated with W-7 or TFP together with serotonin (5-HT; 15 nmol/mouse, IVT), dopamine (DA; 30 nmol/mouse, IVT) or norepinephrine (NE; 30 nmol/mouse, IVT), the sleeping time induced by ethanol and calcium was enhanced. This finding suggests that W-7 and TFP selectively inhibit the synthesis of 5-HT, DA and NE, but they do not affect other neuronal functions of these biogenic amines. The results would suggest a probable mechanism in which Ca++ prolongs ethanol-induced sleeping time by activating tyrosine hydroxylase and tryptophan hydroxylase through intracerebral calmodulin and calmodulin-dependent protein kinase, which subsequently raise the levels of 5-HT, DA and NE.
本研究旨在确定钙对乙醇诱导睡眠的延长作用是否由钙调蛋白和钙调蛋白依赖性蛋白激酶介导。在给予氯化钙（20、40、80和200μmol/kg，腹腔注射（IP））后，测量ddY雄性小鼠乙醇诱导睡眠时间的持续时间，同时给予或不给予钙调蛋白拮抗剂W-7：[N-（6-氨基己基）-5-氯-1-萘磺酰胺]（4.2μg/小鼠，脑室内注射（IVT））或三氟拉嗪（TFP；1.8μg/小鼠，IVT）。当以剂量依赖性方式给予氯化钙时，乙醇诱导的睡眠时间延长。W-7和TFP可拮抗这种延长作用。当小鼠同时接受W-7或TFP与血清素（5-HT；15nmol/小鼠，IVT）、多巴胺（DA；30nmol/小鼠，IVT）或去甲肾上腺素（NE；30nmol/小鼠，IVT）治疗时，乙醇和钙诱导的睡眠时间会延长。这一发现表明，W-7和TFP选择性抑制5-HT、DA和NE的合成，但不影响这些生物胺的其他神经元功能。结果提示了一种可能的机制，即Ca++通过脑内钙调蛋白和钙调蛋白依赖性蛋白激酶激活酪氨酸羟化酶和色氨酸羟化酶，从而延长乙醇诱导的睡眠时间，进而提高5-HT、DA和NE的水平。
