磷脂酰肌醇代谢对中枢烟碱受体功能的调节

目的：研究磷脂酰肌醇代谢中枢烟碱受体功能的调节作用，以分析脑烟碱受体与磷脂酰肌醇代谢之间的关系，方法：在小鼠上观察肌醇磷酸酶抑制剂氯化锂对烟碱诱发发惊厥作用的影响。结果：氯化锂２．５－１０ｍｍｏｌ．ｋｇ＾－１预处理后，烟碱诱发小鼠惊厥的量效关系发生变化，在高于半数效量的剂量下，烟碱诱发惊厥的作用显著增强，但氧颤莫林０．０５－０．２０ｍｇ．ｋｇ＾－１预处理后，烟碱诱发小鼠惊厥的量效关系无显著变化，在     

Modulation of phosphatidylinositol turnover on central nicotinic receptors

目的：研究磷脂酰肌醇代谢对中枢烟碱受体功能的调节作用，以分析脑烟碱受体与磷脂酰肌醇代谢之间的关系．方法：在小鼠上观察肌醇磷酸酶抑制剂氯化锂对烟碱诱发惊厥作用的影响．结果：氯化锂２５－１０ｍｍｏｌ·ｋｇ－１预处理后，烟碱诱发小鼠惊厥的量效关系发生变化，在高于半数效量的剂量下，烟碱诱发惊厥的作用显著增强．但氧颤莫林００５－０２０ｍｇ·ｋｇ－１预处理后，烟碱诱发小鼠惊厥的量效关系无显著变化．在小鼠上每日注射一次氯化锂５０ｍｍｏｌ·ｋｇ－１７ｄ后，烟碱诱发惊厥的作用显著减弱，半数效量由０５８增至０９７ｍｇ·ｋｇ－１．结论：磷脂酰肌醇代谢可调节中枢烟碱受体的功能．     

不同方法炮制槟榔中槟榔碱的含量比较

槟榔为棕榈科,槟榔属植物槟榔Aracate[Aracatechu L]chu,L的种子。临床主要用于杀虫、行气、利水。其主要有效成分为槟榔碱(arecoline C_8 H_(13) O_2 N),槟榔质地坚硬,在药用时,为了提高有效成分的溶出,故对其进行炮制加工。鉴于槟榔碱具有水溶性、脂溶性和随水蒸发的性质。为了探讨几种炮制方法对槟榔碱含量的影响,我们采用中和法对不同方法炮制的槟榔中槟榔碱含量进行了测定比较。 1 仪器及试剂:分析天平,TG328B,分度值:0.1mg。硫酸,氢氧化钠,AR(锦西化学试剂厂)。乙醚、AR(天津市化学试剂二厂)。     

大鼠烟碱依赖对脑皮层M、N胆碱能受体的影响

采用放射配体结合实验，研究大鼠对烟碱形成依赖后脑皮层Ｍ、Ｎ胆碱能受体的变化，结果显示，形成烟碱依赖后脑皮层Ｍ－受体的亲和力与密度均无改变；Ｎ－受体亲和力也无明显变化，而Ｎ－受体密度则从对照组的９０ｆｍｏｌ·ｍｇ－１±ｓ５ｆｍｏｌ·ｍｇ－１蛋白上调到１３１ｆｍｏｌ·ｍｇ－１±ｓ９ｆｍｏｌ·ｍｇ－１蛋白。表明烟碱依赖与脑Ｎ－受体上调相关。     

槟榔碱类似物的合成及活性初筛

以槟榔碱及其丙炔酯为先导化合物，成功地合成了Ｍ胆碱受体配基１１个化合物供筛选。初步药理实验表明部分化合物有较强的Ｍ受体拮抗作用，并对不同器官的Ｍ受体的作用表现出差异性，值得进一步研究，其中七个化合物尚未见文献报道，有三个化合物为首次分离得到。     

反相离子对色谱法测定木香槟榔丸中氢溴酸槟榔碱的含量

目的:建立测定木香槟榔丸中氢溴酸槟榔碱含量的方法。方法:采用反相离子对色谱法测定。色谱柱为Promosil-C18柱,流动相为乙腈-0.1%十二烷基磺酸钠(含0.1%三乙胺,用磷酸调pH=3.8,42:58),流速为1.0mL·min-1,检测波长为215nm,进样量为20μL。结果:氢溴酸槟榔碱浓度在40.4～121.2μg·mL-1范围内与峰面积积分值呈良好线性关系(r=0.9996);平均回收率为100.04%,RSD=1.23%(n=6)。结论:本法灵敏、简便、快速、准确、重复性好,可用于木香槟榔丸的质量控制。     

槟榔碱对小鼠吗啡行为敏化的影响

目的:探讨槟榔嚼块的主要成分—槟榔碱,对小鼠吗啡行为敏化过程的影响。方法:测定小鼠的自主活动,观察ip槟榔碱对小鼠的自主活动及单次给予吗啡所诱导的小鼠高活动性的影响;建立吗啡诱导的小鼠行为敏化模型,观察槟榔碱对行为敏化形成、表达的影响。结果:(1)单次ip槟榔碱(0·25-2·0mg·kg-1)可剂量依赖性地抑制小鼠的自主活动(P<0·05),多次给药后这种抑制作用既不产生耐受,也不形成敏化;(2)槟榔碱(2·0mg·kg-1)可增强单次给予吗啡所诱导的小鼠的高活动性(P<0·05);(3)槟榔碱(2·0mg·kg-1)可增强吗啡诱导小鼠行为敏化的形成(P<0·05);(4)虽然槟榔碱(2·0mg·kg-1)多次给药降低吗啡诱导小鼠行为敏化表达的程度(P<0·05),但是槟榔碱(0·5-2·0mg·kg-1)单次给药不影响吗啡诱导小鼠行为敏化的表达。结论:槟榔嚼块中的主要成分槟榔碱能增强小鼠吗啡诱导的急性高活动性和吗啡行为敏化的形成,提示槟榔嚼块有可能增强吗啡的成瘾性。     

Effects of ethanol, arecoline, atropine and nicotine, alone and in various combinations, on rat cerebellar cyclic guanosine 3',5-monophosphate.

Rat cerebellar cyclic guanosine 3′,5′-monophosphate (cGMP) concentrations were determined by radioimmune methods after sacrifice with focused microwave fixation in animals pretreated with ethanol, arecoline, atropine and nicotine alone and in various combinations. Although arecoline and nicotine treatments resulted in large cerebellar increases in cGMP, they failed to antagonize ethanol's depressive effects. Atropine treatment did not augment ethanol-induced decreases in cGMP content. These data suggest that ethanol's depressant actions on cerebellar cGMP are independent of cholinergic mechanisms.     

槟榔碱增强尼古丁在大鼠海马脑片CA1锥体细胞诱发PS2的作用

在大鼠离体海马脑片上，记录CA1锥体细胞外诱发群峰电位(PS)，以灌流和局部微量注射两种给药途径，观察了槟榔碱(Are)与尼古丁(Nic)同时给药对PS的影响，研究胆碱能M和N受体之间的关系. 结果表明，Are增强Nic诱发第二个群峰电位(PS2)的作用，这一作用不能被M受体拮抗剂阿托品(0.001-0.1 mmol·L^-1)或N受体拮抗剂美卡拉明(1.0 mmol·L^-1)拮抗，兼具中枢胆碱M和N受体拮抗作用的贝那替秦(0.01-0.1 mmol·L^-1)能较好地预防这一作用，表明M和N受体之间存在有相互调节关系.     

槟榔碱增强尼古丁在大鼠海马脑片CA1锥体细胞诱发PS2的作用

在大鼠离体海马脑片上，记录ＣＡ１锥体细胞外诱发群峰电位（ＰＳ），以灌流和局部微量注射两种给药途径，观察了槟榔碱（Ａｒｅ）与尼古丁（Ｎｉｃ）同时给药对ＰＳ的影响，研究胆碱能Ｍ和Ｎ受体之间的关系．结果表明，Ａｒｅ增强Ｎｉｃ诱发第二个群峰电位（ＰＳ２）的作用，这一作用不能被Ｍ受体拮抗剂阿托品（０．００１－０．１ｍｍｏｌ·Ｌ－１）或Ｎ受体拮抗剂美卡拉明（１．０ｍｍｏｌ·Ｌ－１）拮抗，兼具中枢胆碱Ｍ和Ｎ受体拮抗作用的贝那替秦（０．０１－０．１ｍｍｏｌ·Ｌ－１）能较好地预防这一作用，表明Ｍ和Ｎ受体之间存在有相互调节关系．     

Effects of nicotine on levels of acetylcholine and biogenic amines in rat cortex

Transcortical dialysis was employed to investigate the effects of systemic nicotine (3.6 μmol/kg, sc) administration on cortical extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA), and serotonin (5-HT). Systemic administration of [–]-nicotine produced a 106% increase of cortical ACh release over basal levels that persisted for approximately 2 h. Concurrently, NE levels were increased 86% over basal values for 60 min. The effects appear to be stereoselective, as systemic injections of [+]-nicotine significantly increased cortical ACh levels only 48% over basal levels for 30 min, and NE levels in the dialysate only 43% over control levels for 60 min. No significant changes of basal dopamine (DA) or serotonin (5-HT) levels were observed, although DA did appear to increase in response to systemic nicotine. In addition, striatal total endogenous ACh increased significantly over control levels 15 min after [–]-nicotine administration (3.6 μmol/kg, sc), and then significantly declined after 3 h, suggesting that nicotine may influence synthesis as well as release. Analysis of total ACh levels in cortical tissue revealed a similar trend. At the dose utilized in this study, no changes in the cortical electroencephalogram (EEG) were observed. © 1994 Wiley-Liss, Inc.     

Effects of chronic nicotine and haloperidol administration on muscarinic receptor-mediated phosphoinositide turnover in rat brain slices

Muscarinic receptor-mediated phosphoinositide (PI) turnover in rat brain slices was assessed after chronic administration of nicotine (12 mg/kg/day) or haloperidol decanoate (1.5 mg/kg/day), either alone or in combination, for 6 weeks. Nicotine alone did not significantly alter carbachol-induced inositol monophosphate (IP₁) accumulation in the frontal cortex, but did result in a significant increase in the hippocampus, and in a decrease in the striatum. Haloperidol alone attenuated carbachol-stimulated IP₁ accumulation in all three brain regions. Chronic treatment with combined nicotine and haloperidol resulted in no significant change in carbachol-sensitive IP₁ accumulation in either the frontal cortex or hippocampus but did result in a decrease in the striatum. The results suggest significant cross-talk between cholinergic and dopaminergic systems in affecting PI metabolism.     

何首乌饮对衰老模型大鼠下颌下腺组织结构的影响

目的探讨何首乌饮对衰老大鼠下颌下腺组织结构的影响。方法光镜下观察并分别计算经何首乌饮预防或治疗性干预过的亚急性衰老大鼠下颌下腺腺实质、脂肪和纤维间质的相对体积比。结果何首乌饮预防各组腺实质成分所占比例均高于模型组（P〈0.05）。治疗各组腺实质以阴性对照组最高（P〈0.05）,自然恢复组最低（P〈0.05）。伴随衰老,脂肪和纤维间质含量逐渐增多,预防各组间以模型组最高（P〈0.05）；治疗各组间以自然恢复组最高（P〈0.05）,阴性对照组最低（P〈0.05）。结论D-半乳糖模型大鼠下颌下腺功能性腺实质成分逐渐减少而被脂肪和纤维间质所替代。何首乌饮可延缓下颌下腺组织结构的衰老性改变。     

颌下腺动脉及导管的应用解剖学研究

领下腺内的导管、血管、神经及淋巴管由胶原纤维包绕形成了腺实质的核心,我们称之为壳状结构。壳状结构主干呈网状,在此基础上有三级树枝状的分支,分别走行在各级间隔内,两者共同对腺实质起到支持作用。颌下腺动脉可以被概括为三组一支,分别来源于面动脉、颏下动脉及颈外动脉,计5—7支。腺动脉的分支与走行与壳状结构相适应,可作如下分级:腺动脉主干、腺动脉网和三级树枝状分支。对整个颌下腺而言无统一的腺门,但对每个腺叶及腺小叶而言却存在明确的腺门。在壳状结构的主干内管状结构无统一的方向,但在其各级树枝状的分支中却有统一的方向,它们所属的范围是一致的。     

Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine

Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc.     

槟榔碱对大鼠心室肌细胞瞬时外向钾电流的影响

目的：研究槟榔碱(Are)对大鼠心室肌细胞瞬时外向钾电流(I_(to))的影响。方法：利用全细胞膜片钳技术测定大鼠心室肌细胞的I_(to)。结果：10.0μmol·L~(-1) Are可以降低I_(to),使I_(to)幅值从(10.6±s 1.2)pA·pF~(-1)降至(6.2±0.9)pA·pF~(-1)(P＜0.01,n=20)。在1～100μmol·L~(-1)范围内Are的作用呈浓度依赖性,IC_(50)为8.2μmol·L~(-1)。10.0μmol·L~(-1)Are使稳态激活曲线右移,半激活电压(V_(1/2))从(-11.6±0.6)mV移至(-2.3±0.1)mV,但曲线斜率基本不变。Are对失活曲线影响不大,但10.0μmol·L~(-1)Are使通道失活后恢复时间常数从(88±16)ms延长为(152±24)ms(P＜0.01,n=18)。结论：Are浓度依赖地阻滞大鼠心室肌细胞的I_(to)。     

Effects of chlorisondamine on nicotinic receptor binding in whole brain and nicotine-induced changes in locomotor activity in rats

Chlorisondamine, a nicotinic cholinergic receptor antagonist, can block many of the in vivo effects of nicotine for weeks after a single icv injection. The time course of this effect was examined in a single group of rats by assessing the effects of nicotine on locomotor activity at 1, 3, and 6 weeks after the icv administration of 23 nmol of chlorisondamine. The effects of nicotine on locomotor activity were biphasic as has been previously reported, with decreases in activity early in the session and increases in activity later in the session. These effects of nicotine were blocked in chlorisondamine-treated rats at 1 or 3 weeks but not 6 weeks after administration of chlorisondamine. Nicotinic receptor binding in the brains of chlorisondamine-treated rats revealed no change in B_max but a significant increase in affinity (47–59% decrease in K_d) 1, 3, 6, or 7 weeks after treatment. In contrast to its effects on affinity when administered icv, chlorisondamine did not alter binding affinity when added directly to the incubation buffer in vitro. Thus, although chlorisondamine significantly alters neuronal nicotinic cholinergic receptor binding affinity, this effect of chlorisondamine on binding affinity does not appear to be a direct effect of chlorisondamine on the receptor or to match the time course of chlorisondamine blockade of nicotine-induced changes in locomotor activity. © 1994 Wiley-Liss, Inc.