NIK-247通过M2毒蕈碱受体诱导大鼠海马切片CA1区突触传递的长期增强。

NIK-247 induces long-term potentiation of synaptic transmission in the CA1 region of rat hippocampal slices through M2 muscarinic receptors.

Kojima J, Onodera K

Omiya Research Laboratory, Nikken Chemicals Co., Ltd., Saitama, Japan.

Gen Pharmacol. 1998 Aug;31(2):297-300. doi: 10.1016/s0306-3623(97)00436-9.

Abstract

The purpose of this study was to examine whether NIK-247 can, by itself, induce long-lasting changes in synaptic efficacy in the hippocampus. Population spikes evoked by electrical stimulation of the stratum radiatum were recorded in the pyramidal cell layer of the CA1 region of the isolated hippocampus. 2. NIK-247 at 1 x 10(-7) - 1 x 10(-5) M dose dependently increased the amplitude of these spikes. The increase in population spikes by NIK-247 outlasted, for 2 hr, its presence. In addition, the increase in population spikes recovered to 2 hr after washout of NIK-247. Therefore, it was concluded that NIK-247 induced long-term potentiation (LTP) by itself. However, tacrine and physostigmine at 1 x 10(-7) - 1 x 10(-5) M did not increase the amplitude of population spikes and did not induce LTP by themselves. 3. The increase in amplitude of population spikes induced by NIK-247 was completely blocked sensitively by atropine (IC50 = 4.3 x 10(-8)M) but insensitively by pirenzepine (IC50 = 9.1 x 10(-7) M). Carbachol also increased the amplitude of population spikes in the presence of pirenzepine. 4. These findings indicate that the LTP induced by NIK-247 is due to its M2 muscarinic agonistic effect in the CA1 region of the rat hippocampus. It is expected that NIK-247 may be useful for the treatment of Alzheimer disease.

摘要

本研究的目的是检测NIK - 247自身是否能诱导海马体突触效能的持久变化。在分离海马体CA1区的锥体细胞层记录由放射层电刺激诱发的群体峰电位。2. 1×10(-7)-1×10(-5)M剂量的NIK - 247剂量依赖性地增加这些峰电位的幅度。NIK - 247引起的群体峰电位增加在其存在后持续了2小时。此外，在洗去NIK - 247后2小时群体峰电位增加恢复。因此，得出结论：NIK - 247自身诱导了长时程增强（LTP）。然而，1×10(-7)-1×10(-5)M的他克林和毒扁豆碱并未增加群体峰电位的幅度，自身也未诱导LTP。3. NIK - 247诱导的群体峰电位幅度增加被阿托品（IC50 = 4.3×10(-8)M）完全敏感地阻断，但被哌仑西平（IC50 = 9.1×10(-7)M）不敏感地阻断。在存在哌仑西平的情况下，卡巴胆碱也增加了群体峰电位的幅度。4. 这些发现表明，NIK - 247诱导的LTP是由于其在大鼠海马体CA1区的M2毒蕈碱激动作用。预计NIK - 247可能对阿尔茨海默病的治疗有用。