CNS site of action and brainstem circuitry responsible for the intravenous effects of nicotine on gastric tone
CNS site of action and brainstem circuitry responsible for the intravenous effects of nicotine on gastric tone
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DOI：
10.1523/jneurosci.22-07-02764.2002
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发表时间：
2002-04-01
影响因子：
5.3
通讯作者：
Gillis, RA
中科院分区：
文献类型：
--
作者：
Ferreira, M;Sahibzada, N;Gillis, RA
本研究的目的是确定(1)静脉注射的效果。尼古丁对麻醉大鼠胃机械功能的影响：(2)尼古丁对胃机械功能的影响；(3)尼古丁对中枢神经系统烟碱型乙酰胆碱受体(NAChR)亚型(S)的调节作用。尼古丁的作用，以及(4)静脉注射参与的脑干神经回路。尼古丁对胃部有影响。这是通过监测胃内压(胃张力)以及胃底和胃窦的收缩能力来实现的，同时静脉注射五种剂量。尼古丁和向特定脑干核团微量注射尼古丁。此外，静脉注射后c-Fos在脑干中的表达。尼古丁和药理学药物被用来确定中枢神经系统的位置和回路，并揭示了介导尼古丁胃效应的nAChR亚型(S)。使用这些实验方法，我们发现了以下几点。(1)静脉注射尼古丁56.5、113、226、452和904nmol/kg时，仅对胃机械功能有抑制作用。胃对尼古丁最敏感的区域是胃底，这种作用是由迷走神经在56.5、113和226nmol/kg的剂量下介导的。(2)孤束内侧亚核的谷氨酸能迷走传入神经末梢(MNTS)和α4beta2亚型分别是中枢神经系统的作用部位和nAChR亚型。(3)受累的脑干神经回路可能由一条向迷走神经背侧运动核(DMV)投射的去甲肾上腺素通路组成。这一通路似乎是通过迷走释放的谷氨酸激活mNTS中的氮能中间神经元，从而导致α2肾上腺素能受体介导的抑制DMV神经元投射到眼底和控制胃张力。
The purposes of our study were to determine (1) the effects of intravenous (i.v.) nicotine on gastric mechanical function of anesthetized rats, (2) the CNS site of action of nicotine to produce these effects, (3) the CNS nicotinic acetylcholine receptor (nAChR) subtype(s) responsible for mediating the i.v. effects of nicotine, and (4) the brainstem neurocircuitry engaged by i.v. nicotine for eliciting its gastric effects. This was accomplished by monitoring intragastric pressure (gastric tone) and contractility of the fundus and antrum while administering five doses of i.v. nicotine and microinjecting nicotine into specific brainstem nuclei. Additionally, c-Fos expression in the brainstem after i.v. nicotine and pharmacological agents were used as tools to identify the CNS site and circuitry and reveal the nAChR subtype(s) mediating the gastric effects of nicotine. Using these experimental approaches, we found the following. (1) When given intravenously in doses of 56.5, 113, 226, 452, and 904 nmol/kg, nicotine elicited only inhibitory effects on gastric mechanical function. The most sensitive area of the stomach to nicotine was the fundus, and this effect was mediated by the vagus nerve at doses of 56.5, 113, and 226 nmol/kg. (2) The CNS site of action and nAChR subtype responsible were glutamatergic vagal afferent nerve terminals in the medial subnucleus of the tractus solitarious (mNTS) and alpha4beta2, respectively. (3) The brainstem neurocircuitry that was involved appeared to consist of a mNTS noradrenergic pathway projecting to the dorsal motor nucleus of the vagus (DMV). This pathway seems to be activated via nitriergic interneurons engaged by vagally released glutamate in the mNTS and results in alpha2 adrenergic receptor-mediated inhibition of DMV neurons projecting to the fundus and controlling gastric tone.