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51.
Calcium mobilization elicited by two types of nicotinic acetylcholine receptors in mouse substantia nigra pars compacta 总被引:11,自引:0,他引:11
Tsuneki H Klink R Léna C Korn H Changeux JP 《The European journal of neuroscience》2000,12(7):2475-2485
Nicotinic acetylcholine receptors (nAChRs) are expressed in the midbrain ascending dopaminergic system, a target of many addictive drugs. Here we assessed the intracellular Ca2+ level by imaging fura-2-loaded cells in substantia nigra pars compacta in mouse brain slices, and we examined the influence on this level of prolonged exposures to nicotine using mice lacking the nAChR beta2-subunit. In control cells, superfusion with nicotine (10-100 microM) caused a long-lasting rise of intracellular Ca2+ level which depended on extracellular Ca2+. This nicotinic response was almost completely absent in beta2-/- mutant mice, leaving a small residual response to a high concentration (100 microM) of nicotine which was inhibited by the alpha7-subunit-selective antagonist, methyllycaconitine. Conversely, the alpha7-subunit-selective agonist choline (10 mM) caused a methyllycaconitine-sensitive increase in intracellular Ca2+ level both in wild-type and beta2-/- mutant mice. Nicotine-elicited Ca2+ mobilization was reduced by the Na+ channel blocker tetrodotoxin (TTX) and by T-type Ca2+ channel blocking agents, whereas the choline-elicited Ca2+ increase was insensitive to TTX. Neither nicotine nor choline produced Ca2+ increase following inhibition of the release of Ca2+ from intracellular stores by dantrolene. These results demonstrate that in nigral dopaminergic neurons, nicotine can elicit Ca2+ mobilization via activation of two distinct nAChR subtypes: that of beta2-subunit-containing nAChR followed by activation of Na+ channel and T-type Ca2+ channels, and/or activation of alpha7-subunit-containing nAChR. The Ca2+ influx due to nAChR activation is subsequently amplified by the recruitment of intracellular Ca2+ stores. This Ca2+ mobilization may possibly contribute to the long-term effects of nicotine on the dopaminergic system. 相似文献
52.
Allen DD Martín J Arriagada C Cárdenas AM Rapoport SI Caviedes R Caviedes P 《The European journal of neuroscience》2000,12(9):3259-3264
Murine trisomy 16 is an animal model of human Down's syndrome. We have successfully established permanently growing cell lines from the cerebral cortex of normal and trisomy 16 foetal mice using an original procedure. These lines, named CNh (derived from a normal animal) and CTb (derived from a trisomic foetus), express neuronal markers. Considering that Down's syndrome exhibits cholinergic deficits, we examined cholinergic function in these lines, using incorporation of [3H]-choline and fractional release studies. After 1, 3 and 5 min of [3H]-choline incubation, CTb cell uptake was lower by approximately 50% compared to controls. Hemicholinium-3 significantly reduced the incorporation of [3H]-choline in both CNh and CTb cells at high concentration (10 microM), suggesting high-affinity choline transport. However, CTb cells exhibited greater sensitivity to the blocker. For fractional release experiments, the cells were stimulated by K+ depolarization, glutamate or nicotine. When depolarized, CTb cells showed a 68% reduction in fractional release of [3H]-acetylcholine compared to CNh cell line, and a 45% reduction when stimulated by nicotine. Interestingly, glutamate induced similar levels of release in both cell types. The results indicate the existence of cholinergic dysfunction in CTb cells when compared to CNh, similar to that reported for primary cultures of trisomy 16 brain tissue (Fiedler et al. 1994, Brain Res., 658, 27-32). Thus, the CTb cell line may serve as a model for the study of Down's syndrome pathophysiology. 相似文献
53.
内皮细胞乙酰胆碱靶标不同于M受体的药理学特征 总被引:4,自引:4,他引:4
目的 研究内皮细胞乙酰胆碱靶标与M受体药理学特征的差异。方法 采用离体血管环实验方法,观察抗M_3受体的单克隆抗体和M受体激动剂毛果芸香碱对乙酰胆碱引起的内皮依赖性舒张血管作用的影响。结果 毛果芸香碱能够剂量依赖性拮抗乙酰胆碱诱导的内皮依赖性血管舒张作用,其拮抗性质为非竞争性拮抗;抗M_3受体的单克隆抗体不影响乙酰胆碱诱发的内皮依赖性舒张血管作用,但能拮抗乙酰胆碱诱发的离休肠肌收缩作用。结论 内皮细胞乙酰胆碱靶标的药理学特征不同于经典M受体。 相似文献
54.
目的 研究雌性大鼠卵巢切除和雌激素替代治疗 4个月后 ,血管活性物质对离体动脉作用的改变。方法 采用双侧卵巢切除的雌性大鼠 ,分为假手术组、去卵巢组 (8周龄切除双侧卵巢 )和雌激素替代组 (苯甲雌二醇 40 μg,sc ,每日 1次 ,卵巢切除后 1 4d开始给药至切除后 4个月 )。于给药结束时取升主动脉、胸主动脉及尾动脉 ,进行离体血管功能实验 ,观察对降钙素基因相关肽 (CGRP)、乙酰胆碱(ACh)及去甲肾上腺素 (NE)的反应。结果 卵巢切除 4个月使CGRP引起的大鼠升主动脉舒张最大效应明显降低 ,而对胸主动脉无影响 ;同时ACh对胸主动脉的舒张效应曲线明显右移 ,而对升主动脉无影响。雌激素替代治疗使上述变化反转。去卵巢组的各类动脉对NE的反应性无变化 ,而雌激素替代组的升主动脉和胸主动脉对NE引起的最大收缩效应明显降低。在尾动脉 ,去卵巢组和雌激素替代组的CGRP和NE反应性均无改变。结论 内源性雌激素可以通过多种途径调节血管反应性 ,发挥其心血管保护作用。本研究进一步提示对绝经期妇女进行激素替代治疗的重要性 相似文献
55.
Objective: To observe the behavioral and biochemical effects of a traditional Chinese medicine Huanshao Dan (HSD) on learning and memory
deficits in transient cerebral ischemia model in mice.Methods: Step-through experiments, receptor binding test and choline acetyltransferase (ChAT) activities determination were performed.Results: Mice undertaken transient ischemia commited much more mistakes in step-through experiments and showed relatively higher3 H-MK801 binding in cerebral cortex and hippocampus than in sham operated animals. HSD decoction was most effective in reducing
these mistakes in mice. At the same time, and3 H-MK801 binding of cerebral cortex and hippocampus tissues were also significantly decreased, while ChAT activities in the
same tissues were increased.Conclusion: HSD might antagonize ischemic injury of brain through inhibition of glutamate N-methyl-D-Aspartic acid receptor overactivity.
ΔThis program was supported by National Nature Science Foundation of China (No.39421012) 相似文献
56.
目的:测定氯化琥珀胆碱注射液中氯化胆碱与氯化琥珀胆碱含量。方法:以固定化胆碱氧化酶(EC5896)结合H2O2电极构成电流型酶电极生物传感分析仪并与银量法对比测定。结果:酶电极法测定线性范围:0mg·L-1~200mg·L-1,精度RSD<1.5%,响应时间:40s,固定化胆碱氧化酶膜使用寿命大于60d,实际测定氯化琥珀胆碱注射液中氯化胆碱含量;回收率:100.3%~102.3%。与银量法对比测定,两法测定结果的相关系数r=0.9929。结论:采用酶电极法能准确测定氯化琥珀胆碱注射液中氯化胆碱及氯化琥珀胆碱含量。 相似文献
57.
目的观察孕酮对东莨菪碱所致记忆损伤小鼠的作用及机制。方法东莨菪碱(1mg·kg-1,ip)造成小鼠记忆损伤模型,利用被动逃避实验评价小鼠记忆成绩,并测定给药后24h小鼠皮质和海马胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)的活性。结果在被动逃避实验中,东莨菪碱造成小鼠记忆损伤,孕酮(1、10mg·kg-1,sc)预处理能减少跳台错误次数(P<0.05),延长跳台潜伏期(P<0.01)和避暗潜伏期(P<0.01)。东莨菪碱增加皮质和海马AChE活性,降低ChAT活性,孕酮(1mg·kg-1,sc)预处理抑制皮质和海马AChE活性的增加(P<0.01),升高皮质(P<0.05)和海马(P<0.01)ChAT活性。结论孕酮可以改善东莨菪碱所致记忆损伤,机制可能与其抑制皮质和海马AChE活性、升高ChAT活性有关。 相似文献
58.
59.
三七总皂苷对Alzheimer''''s病大鼠模型大脑胆碱能神经病理损害的保护作用 总被引:15,自引:0,他引:15
目的:观察三七总皂苷(PNS)对老年性痴呆(AD)大鼠模型大脑胆碱能神经病理损害的保护作用.方法:以d-半乳糖腹腔注射致亚急性损伤合并鹅膏蕈氨酸(IBA)损毁双侧大脑Meynert基底核建立AD大鼠动物模型,利用免疫组织化学方法检测大脑切片胆碱乙酰基转移酶(ChAT)免疫反应活性及阳性神经元数量及形态学改变.结果:PNS能明显减轻由d-半乳糖损害和鹅膏蕈氨酸损毁导致的大脑胆碱能神经元数量减少和ChAT水平降低.结论:PNS对AD大鼠模型大脑胆碱能神经的病理损害具有保护作用. 相似文献
60.
Neurochemical effects of repeated gestational exposure to chlorpyrifos in developing rats. 总被引:1,自引:0,他引:1
The neurochemical effects in developing rats exposed during gestation to the anticholinesterase organophosphorus insecticide chlorpyrifos (CPS) were determined. Pregnant rats were dosed daily with CPS (0, 3, or 7 mg/kg) in corn oil from gestation days (GD) 6-20. Pups were euthanized on postnatal days (PND) 1, 3, 6, 9, 12, and 30 for the determination of brain cholinesterase (ChE) and choline acetyltransferase (ChAT) activities, along with muscarinic receptor (mAChR) densities, the levels of the high-affinity choline uptake (HACU) system, and the vesicular acetylcholine transporter (VAChT). ChE activities were inhibited about 15 and 30% on PND 1, in the low- and high-dosage groups, respectively, and were not different from control values by PND 6. mAChR densities on PND 1 were reduced in the high-dosage group by about 18, 21, and 17%, using 3H-N-methylscopolamine, 3H-quinuclidinyl benzilate, and 3H-4-DAMP, respectively, as ligands, and were not different from control levels by PND 6. ChAT activity was decreased by approximately 12% in the high-dosage group on PND 9, 12, and 30. HACU levels, using 3H-hemicholinium-3 as the ligand, were reduced by approximately 25% on PND 6 in the low- and high-dosage groups, and by approximately 14 and 21% on PND 12 and 30, only in the high-dosage group. Levels of the VAChT were reduced by a range of 13-31% on PND 3 through 30 in the high-dosage group, using 3H-AH5183 (vesamicol) as the ligand. These data suggest that gestational exposure to 7 mg/kg/day CPS results in long-term alterations of presynaptic cholinergic neurochemistry. 相似文献