Compartmentation of catecholamines in rat brain: Effects of agonists and antagonists

The subsynaptosomal distributions of dopamine (DA) in striatum and of norepinephrine (NE) in hypothalamus and cerebral cortex were examined. Isolated nerve-endings from each region were osmotically disrupted and subractionated into a soluble cytoplasmic fraction (end supernatant, Se) and a synaptic vesicle fraction (P₂V). DA and NE were measured in the crude homogenate and in subcellular fractions by a radioenzymatic assay. Levels of NE and DA were 3–5 times higher in the nerve-ending cytoplasm than in the synaptic vesicles, suggesting that catecholamines within the nerve-endings are predominantly in soluble form. Amphetamine increased DA levels in the tissue homogenate and in the nerve-ending cytoplasm but not in synaptic vesicles. Pargyline and γ-butyrolactone (GBL) increased DA levels in all fractions with the greatest increase occuring in the cytoplasmic fraction. Both 6-hydrodopamine (6-OHDA) and α-methyltyrosine (AMT) cuased uniform DA decreases in all fractions. Hypothalamic levels of NE in the two nerve-ending compartments were also reduced to a similar extent after AMT. Reserpine produced uniform depletions of striatal DA in both nerve-ending fractions while the rate of DA repletion was more rapid in the vesicular compartment. Levels of hypothalamic NE were also uniformly depleted by reserpine at the times examined. The cytoplasmic storage compartment is discussed in terms of a possible anatomical correlate such as the smooth endoplasmic reticulum.     

Reduction by reserpine of the accumulation of retrogradely transported [I]nerve growth factor in sympathetic neurons

Experiments were carried out to determine if stimuli which augment preganglionic nerve activity to sympathetic neurons, and thereby cause trans-synaptic induction, increase the retrograde transport of nerve growth factor (NGF). It was found that nerve activity had no effect on retrograde transport of [¹²⁵I]NGF. It was found, however, that reserpine decreased retrograde transport of [¹²⁵I]NGF and this inhibition was characterized. Reserpine decreased the maximal accumulation of intravenously administered[¹²⁵I]NGF in superior cervical ganglia (SCG) by about 60%. It also caused a distinct shift in the time course of accumulation so that maximal accumulation was seen 12 h after [¹²⁵I]NGF injection rather than at 9 h as in control animals. Reserpine had no effect on retrograde transport in sensory neurons. Dose-response curves showed that maximal inhibition occurred with doses of reserpine of 2.5 mg/kg i.p. and that reserpine was not able to completely block transport at any dose.The maximal inhibition of retrograde transport was achieved within 30 min of reserpine administration and inhibitory activity was unchanged for 36 h. The ability of sympathetic neurons to transport [¹²⁵I]NGF subsequently recovered and was normal 96 h after reserpine administration. The inhibitory effect of reserpine appears to be due to an action at or very near to the nerve terminal since it was effective at reducing NGF transport at very low doses (0.33 μg) when co-administered directly into the eye with [¹²⁵I]NGF. An action of reserpine at the nerve terminal was further suggested by the inability of reserpine to affect transport if the drug was given 4 h after [¹²⁵I]NGF administration. Based upon these data, it is suggested that there may be two pools of retrogradely transported NGF and that only more rapidly turning over pool is reserpine-sensitive. This pool may represent the retrogradely moving synaptic vesicles or some derivative of the vesicles.     

Detour learning in the chick: Effect of reserpine administered during embryonic development

Chicks hatched from eggs injected with reserpine prior to incubation showed impaired performance in detour learning between 7 and 17 days of age, although locomotor activity and brainstem catecholamine levels were not significantly different from controls at 18 days. Day-old chicks injected with the same amount of drug showed no significant depletion of brainstem catecholamines 7 days later, supporting the possibility that behavioral effects were due to exposure to the drug during embryogenesis.     

马来酸三甲氧苯丁氨酯镇痛机制的初步研究

对马来酸三甲氧苯丁氨酯（ＴＭ） 镇痛作用的机制进行了初步探讨．结果显示,脑室内注射ＴＭ４０ 、８０ μｇ／ 鼠能够显著抑制小鼠扭体反应,表明ＴＭ 的镇痛作用有中枢参与．利血平、纳洛酮能够减弱ＴＭ 的镇痛作用,ＣａＣｌ２ 和ＥＤＴＡ 则分别减弱和增强其镇痛作用．表明ＴＭ 的镇痛作用可能与阿片系统,中枢单胺类递质及钙离子浓度有关     

复方降压片对高血压大鼠冠状动脉壁肥厚和储备力下降的影响

目的 研究复方降压片对高血压大鼠冠状动脉壁肥厚和储备力下降的影响。方法 4w大鼠设4组：分别为自发性高血压大鼠(SHR)组、SHR口服复方降压片组、SHR口服卡托普利组和正常血压大鼠(WKY)组，饲养12w。冠脉最大血流量用离体心脏灌注法测定。结果 复方降压片能显著降低SHR收缩压、冠状动脉横截面积，提高最大冠状动脉流量，与卡托普利相似。复方降压片能降低SHR的左心室重与体重比，但仍然显著高于WKY组和口服卡托普利组。结论 复方降压片能预防SHR冠状动脉壁肥厚、储备力下降，减轻左心室肥厚；冠状动脉血流储备力的损害程度和左心室肥厚程度不平行。     

Modification of reserpine-induced emetic response in pigeons by α2-adrenoceptors

In the present study, an attempt has been made to elucidate the role of α₂-adrenoceptors in reserpine-induced emesis in pigeons. Reserpine was found to induce dose-dependent emesis and a 500 jug kg⁻¹ dose was found to be the 100% emetic dose. a2-adrenoceptor agonists clonidine and a-methylnoradrenaline inhibited the reserpine induced emesis. Out of the two selective a2-adrenoceptor antagonists idazoxan and yohimbine, only the latter induced a dose-dependent emesis. However, both the drugs potentiated reserpine-induced emesis and antagonised its inhibition by clonidine. Prior depletion of monoamines by reserpine also blocked the emetic response of reserpine. These observations indicate that release of monoamines is responsible for its emetic response in pigeons which is modulated by presynaptic a,-adrenoceptors in a predictable manner.     

囊泡单胺类转运体功能抑制对PC12细胞凋亡的影响

目的：研究帕金森病黑质多巴胺神经元的死亡机理。方法：用四甲基偶氮唑盐（MTT）法及流式细胞仪观察囊泡单胺类转运（VMAT）功能抑制对大鼠嗜铬细胞瘤（PC12）细胞凋亡的影响。结果：单独作用的VMT抑制剂和利血平对PC12细胞无毒性作用，超过一定浓度的多巴胺（0．3mmol/L）对PC12细胞有毒性作用，利血平协同钦巴胺明显增加多巴胺的毒性，使同伴浓度的多巴胺诱发PC12细胞的凋亡率明显增加，致使较低浓度的多巴胺（0．15mmol/L）就可降低PC12细胞生存率，结论：VMAT功能抑制引发了多巴胺的内源性毒性，进而诱发多巴胺神经元的凋亡，可较好地解释帕金森病的发病机理。     

儿茶酚胺在急性心肌梗塞时血液流变学变化中的意义

应用利血平耗竭体内儿茶酚胺和肾上腺切除法制造急性心肌梗塞（ＡＭＩ）模型，发现ＡＭＩ后出现的血粘度升高，红细胞变形能力下降，红细胞压积升高，血浆粘度升高及红细胞聚集性增强等血液流变学变化是交感－肾上腺髓质系统兴奋所致。其中红细胞压积增加的主要原因是交感神经兴奋，而其它改变可能为交感神经肾上腺髓质共同作用的结果     

The antidepressant effect of agnmtine in pharmacological depression models

AIM To explore the antidepressant effects and its possible mechanism of agmatine （AGM） in pharmacological depression models. Methods The 5 -hydroxytryptophan potentiation test, yohimbine toxicity potentiation test, apomorphine-induced hypothermia test and reseponie-induced hypothermia test in mice were used in this study. Results Repeated administration with AGM（10,20,40,80mg. kg^-1 ,     

吗氯贝胺抗抑郁作用的实验研究

用大鼠和小鼠行为失望实验及抗利血平致眼睑下垂试验观察了吗氯贝胺１的抗抑郁效应。结果表明１能减少大鼠行为失望试验的游泳不动时间，能对抗利血平引起的眼睑下垂，并有良好的量效关系。此外，１能增强５－羟色氨酸引起的震颤及左旋多巴引起的奔跑行为。