Takahashi M, Morinobu S, Totsuka S, Endoh M
Department of Neuropsychiatry, School of Medicine, Yamagata University, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1996 May;353(6):616-20. doi: 10.1007/BF00167180.
The present study was undertaken to investigate the effects of chronic administration of dexamethasone on the noradrenaline- and serotonin-stimulated (5-HT-stimulated) phosphoinositide metabolism in hippocampus and frontal cortex of the rat brain. For determination of phosphoinositide metabolism, slices from selected regions of the rat brain (hippocampus or frontal cortex) were loaded with myo- [3H] inositol and stimulated with the agonists (noradrenaline or 5-HT) in the presence of LiCl (7.5 mM). Administration of dexamethasone (1 mg/kg/day) every 2nd day for 14 days markedly reduced the noradrenaline-stimulated phosphoinositide metabolism in the rat hippocampus (IP1: 60% of the control value). In the rat frontal cortex, the noradrenaline-stimulated phosphoinositide metabolism was less depressed by the chronic administration of dexamethasone (IP1: 84% of the control value). However, the chronic administration of dexamethasone did not affect the 5-HT-stimulated phosphoinositide metabolism in the rat brain. The binding characteristics of alpha 1 -adrenoceptors and 5-HT2A receptors were unaffected by the chronic treatment with dexamethasone. These results indicate that chronic administration of dexamethasone induces regional and neurotransmitter-specific changes of phosphoinositide metabolism in rat brain. The results suggest that the reduction of noradrenaline-stimulated phosphoinositide metabolism is due to modification of the intracellular signal transduction system.
本研究旨在探讨长期给予地塞米松对大鼠脑海马和额叶皮质中去甲肾上腺素和5-羟色胺（5-HT）刺激的磷酸肌醇代谢的影响。为了测定磷酸肌醇代谢，从大鼠脑的选定区域（海马或额叶皮质）获取切片，用肌醇-[3H]进行标记，并在存在LiCl（7.5 mM）的情况下用激动剂（去甲肾上腺素或5-HT）进行刺激。每隔一天给予地塞米松（1 mg/kg/天），持续14天，可显著降低大鼠海马中去甲肾上腺素刺激的磷酸肌醇代谢（IP1：为对照值的60%）。在大鼠额叶皮质中，长期给予地塞米松对去甲肾上腺素刺激的磷酸肌醇代谢的抑制作用较小（IP1：为对照值的84%）。然而，长期给予地塞米松并不影响大鼠脑中5-HT刺激的磷酸肌醇代谢。α1-肾上腺素能受体和5-HT2A受体的结合特性不受地塞米松长期治疗的影响。这些结果表明，长期给予地塞米松可诱导大鼠脑内磷酸肌醇代谢的区域和神经递质特异性变化。结果提示，去甲肾上腺素刺激的磷酸肌醇代谢的降低是由于细胞内信号转导系统的改变所致。
