Does ornithine stimulate carbamoylphosphate synthetase?

The effect of ornithine on carbamoylphosphate formation of rat liver mitochondria treated with Triton X 100 was studied. The rate of carbamoylphosphate accumulation and citrulline formation depended on the ATP-, Pi-, N-acetylglutamate and protein concentration. At optimal conditions the rate of citrulline formation was at least 1.5-fold higher than the rate at which carbamoylphosphate accumulated (ornithine absent). A significant correlation between the amount of carbamoylphosphate formed and the citrulline/carbamoylphosphate ratio (ornithine effect) was found. In mitochondria the presence of a carbamoylphosphate degrading enzyme could be demonstrated. This enzyme may be one factor for the differences in the rate of carbamoylphosphate accumulation and the rate of citrulline synthesis.     

GABA对小鼠大脑皮质中GABA受体胚胎发育的调节

本文用ＧＡＢＡ及其受体激动剂和拮抗剂处理培养的胚胎小鼠大脑皮层神经细胞以及精确计时的妊娠小鼠,用放射配体结合法检测ＧＡＢＡＡ及ＧＡＢＡＢ的结合位点数目,研究了ＧＡＢＡ对小鼠大脑皮层ＧＡＢＡ受体胚胎发育的调节作用,结果表明：①ＧＡＢＡ可使培养１５—１７天妊龄的胚胎小鼠大脑皮层神经细胞及出生第１天的仔鼠大脑皮层中的ＧＡＢＡＡ及ＧＡＢＡＢ受体数目增加,这种作用可被蝇蕈醇（Ｍｕｓ）及巴氯芬（Ｂａｃ）分别模拟,对ＧＡＢＡＡ受体的作用可为荷包牡丹碱（Ｂｉｃ）所阻断;②用ＧＡＢＡ处理妊娠７—１３天的小鼠,仔鼠出生第１天其大脑皮层的ＧＡＢＡＡ及ＧＡＢＡＢ受体数目均无变化;③用ＧＡＢＡ处理妊娠１４—１９天的小鼠,仔鼠出生的第１天其大脑皮层中的ＧＡＢＡＡ受体数目增加而ＧＡＢＡＢ受体数目不变;④用ＧＡＢＡ处理妊娠７－１９天的小鼠,仔鼠出生第１天其大脑皮层中ＧＡＢＡＡ及ＧＡＢＡＢ受体数目增加。这说明在胚胎发育的特定时期内,ＧＡＢＡ可诱导其受体数目的增加,这个作用是由ＧＡＢＡ受体调节的。     

Effects of γ-acetylenic GABA and γ-vinyl GABA on electrically-induced spinal cord convulsions and on spinal cord GABA concentration

The effects of γ-acetylenic GABA and γ-vinyl GABA on electrically-induced spinal cord convulsions were compared to the effects of these same drugs on spinal cord GABA concentration. The data show that the effects of these two compounds on seizure activity do not correlate either positively or negatively with changes in GABA concentration. Although both drugs produced marked increases in the amount of GABA in the spinal cord, their effects on spinal cord convulsions were qualitatively different and failed to correlate temporally with alterations in GABA concentration.     

Is cyclic AMP the regulator of hepatic ornithine decarboxylase activity?

The role of cyclic AMP in the regulation of hepatic ornithine decarboxylase (ODC) activity in the rat was studied in the whole animal and in the perfused organ. Dibutyryl cyclic AMP or butyrate given to intact rats increased ODC activity; this increase was abolished by hypophysectomy 1 h prior to administering ether compound. Administration of 1 mg 1-methyl-3-isobutylxanthine (MIX) to intact rats increased ODC activity within 4 hours whereas hypophysectomy 1 h before treatment prevented this increase. No change in hepatic cyclic AMP content was seen in either intact or hypophysectomized rats following MIX. Perfusion with 0.5 mM dibutyryl cyclic AMP decreased ODC activity in isolated livers whereas perfusion with 0.5 mM 8-bromocyclic GMP produced a small increase in ODC activity. These data suggest that the effect of dibutyryl cyclic AMP in intact animals may be a property of the butyrate and that this action as well as the action of MIX may be mediated through the permissive effect of pituitary and/or adrenal hormones. The normal hepatocyte does not increase its ornithine decarboxylase activity after direct exposure to dibutyryl cyclic AMP.     

GABA 能系统与失眠

γ-氨基丁酸(GABA)是一种重要的抑制性神经递质,众多研究表明,GABA能系统功能异常与失眠以及焦虑,抑郁等情感障碍关系密切。焦虑,抑郁等神经心理异常可能是引发失眠的原因之一。本文总结了GABA能系统与失眠及情感障碍关系,为治疗失眠提供新的理论依据。     

Inhibition of EMT6 tumor growth by interference with polyamine biosynthesis ; Effects of α-difluoromethyl- ornithine,an irreversible inhibitor or ornithine decarboxylase

α-Difluoromethylornithine (α-DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC), retarded the growth rate of EMT6, a murine mammary sarcoma, in tissue culture. When female BALB/_C mice were inoculated subcutaneously with EMT6 cells, administration of α-DFMO as a 3% solution in the drinking water beginning 5 days after tumor inoculation resulted in an 80% inhibition of tumor weight gain by day 27 compared to controls. This treatment regimen, equivalent to 4.4 g α-DFMO/kg/day, decreased tumor ODC activity, stimulated S-adenosyl-L-methionine decarboxylase (SAM-DC) activity and markedly decreased tumoral putrescine and spermidine, but not spermine, concentrations. The tumor growth inhibitory effects of α-DFMO were similar to those obtained with 4 weekly doses of cyclophosphamide (100 mg/kg i.p. beginning on day 6 post-inoculation). The combination of cyclophosphamide plus α-DFMO caused the same or greater inhibition of tumor growth than either treatment alone. When the SAM-DC and diamine oxidase inhibitor, 1,1'-((methylethanediylidene)-dinitrilo) bis (3-amino-guanidine), was added to α-DFMO treatment, tumor SAM-DC activity, putrescine and spermidine concentrations, but not ODC activity, returned to control values and the anti-proliferative effects of α-DFMO were reversed. These results suggest that α-DFMO treatment is an effective non-toxic method of inhibiting tumor growth by a mechanism involving polyamine depletion.     

Effect of di-n-propylacetate and γ-acetylenic GABA on hyperbaric oxygen-induced seizures and GABA metabolism

The administration of -acetylenic GABA or di-n-propylacetate to mice delayed the onset of hyperbaric oxygen-induced seizures in the animals. The former compound caused large increases in brain GABA content and strong inhibition of glutamate decarboxylase activity, whereas the latter compound brough about only moderate increases in brain GABA level and had little or no effect on the enzyme activity. It is suggested that the GABA system is not involved in the anticonvulsant mechanism of -acetylenic GABA but may play a role in the action of di-n-propylacetate.     

GABA能神经功能有了新发现

美国耶鲁大学S.A.Tomiko等最近以电生理实验表明,GABA通过荷包牡丹碱(bicuculline,BC)-阻滞性受体,直接作用分离出的大鼠促黑激素(MSH)细胞,结果Cl~-电导增加,膜电位朝Cl~-平衡电位的方向发展,引起静息部位去极化或使高K~ 诱发的去极化难以进行。作者发现GABA首先刺激MSH释放,尔后抑制之,同时抑制K~ 诱发的MSH分泌。作者提供的药理学证据提示,上述分泌和电生理活动所涉及的受体相同。GABA能神经直接作用MSH细胞,改变其释放量,并受GABA产生的电生理特性的变化而影响其功能,这是GABA能神经功能的新发现。多采用大鼠为实验对象,先分离垂体后叶中间部细胞,体外短期培养,并置于柱形器皿内,持续灌流并测定MSH释放量。     

GABA and “neuro-cardiovascular” mechanisms

One has only to recall that GABA appears to be a major inhibitory neurotransmitter in the vertebrate central nervous system (CNS), that it exerts a hypotensive action upon systemic administration, that it is present in the blood, that its actions are antagonized by bicuculline and picrotoxin and facilitated by benzodiazepines, and that receptors for GABA exist in cerebral blood vessels, to consider that GABA is somehow involved in cardiovascular regulation. One might even postulate that influences upon GABA-ergic mechanisms are involved in that dangerous sequence of biological activities: environmental stress → anxiety → atherosclerosis and hypertension, the latter of which represent major health problems of man. Herein, some evidence that appears to support this view will be presented.     

GABA对热应激仔鸡的影响

将一周龄的“882”肉仔鸡 ,随机分为 2组。让对照组仔鸡饮用蒸馏水 ,让试验组饮用 0 0 5 %的氨酪酸 (GABA)蒸馏水。 2组每天置于 32℃的箱中热处理 1 5h ,试验 4周。结果表明GABA对热应激肉仔鸡有一定的影响 :试验组仔鸡的呼吸频率极显著低于对照组 (P <0 0 1) ;红细胞数显著高于对照组 (P <0 0 5 ) ;料重比极显著低于对照组 (P <0 0 1) ,仔鸡增重是对照组鸡的 117 86 % (P <0 0 5 )。     

GABA及BZD受体与肝脑病

GABA及BZD受体γ-氨基丁酸(γ-aminobutyric acid,GABA)是中枢神经系统的主要抑制性递质,它的抑制效应是通过兴奋GABA受体而实现的。根据GABA受体对药物的不同选择性,可分为GABA_A和GABA_B两种受体,前者又可进一步分成GABA_(A-1)、GABA_(A-2)及GABA_(A-3)等亚型。自1984年以来,国际上有几家实验室用各种现代技术(如分子生物学、免疫亲和层析等技术)来提取和纯化动物脑内的GABA受体。目前已了解到GABA_A受体是一个四聚体,分别有2个α及2个β亚单位构成。现已能人工合成GABA_A受     

GABA受体与药物依赖性的研究进展

药物成瘾是一种全球性的公共卫生问题,其发生机制十分复杂。γ-氨基丁酸(γ-aminobutyric acid,GABA)是中枢神经系统中主要的抑制性神经递质,其通过调节GABA受体(如:GABA_A,GABA_B)的活性参与多种药物成瘾和依赖性的发生与发展过程。吗啡、可卡因、甲基苯丙胺等药物引起的奖赏、戒断和复吸作用与GABA受体的激活或抑制密切相关。本文将对GABA受体在药物依赖中的作用及机制进行综述,从而为治疗药物成瘾提供新的策略。     

GABA神经元在金黄地鼠视觉中枢的分布

本文用免疫细胞化学技术研究了GABA在金黄地鼠视觉中枢的分布特征,同时用统计学方法作了定量分析,结果表明:GABA阳性神经元分布在整个视皮层和上丘中,呈不均匀分布,外膝体中GABA阳性神经元密度较低.视皮层中GABA阳性神经元密度为781mm~2,占视皮层细胞总数的19.7%,上丘中其密度为812/mm~2,占22.3%,视皮层Ⅰ层中GABA阳性神经元为52%,上丘表层(浅灰层及视觉层GABA阳性神经元为56%,GABA阳性神经元包括不同类型的细胞.在视皮层中可观察到GABA免疫疫应阳性的锥体细胞.     

Autoradiographic localization of ornithine decarboxylase in mouse kidney by use of radiolabeled α-difluoromethylornithine

Summary Ornithine decarboxylase, a key enzyme in polyamine biosynthesis and cell growth, has been localized in mouse kidney by autoradiography after administration of radiolabeled -difluoromethylornithine. This drug is an enzyme-activated irreversible inhibitor of ornithine decarboxylase and forms a covalent bond with the enzyme. It was found that ornithine decarboxylase is present in all cell types studied but that the highest content occurs in the proximal convoluted tubules followed by the distal convoluted tubules and the collecting tubules. The majority of the enzyme is located in the cytoplasm but about 10–15% is present in the nuclei (often associated with nucleolus-like components) of the cells of the proximal and distal convoluted tubules. The labeled ornithine decarboxylase was lost rapidly from both nucleus and cytoplasm of all the cell types examined, and labeling by radioactive -difluoromethylornithine was greatly reduced if the mice were pretreated for 5 h with cycloheximide to block protein synthesis. These results indicate that ornithine decarboxylase turns over rapidly in all of the cells.     

GABA能神经元在鸽峡核中的分布

本文用免疫细胞化学技术研究了r-氨基丁酸(GABA)阳性神经元在家鸽(Columba livia)峡核中的分布特点.实验结果表明,GABA阳性神经元在峡核大细胞部(Imc)呈均匀分布.约占细胞总数的41%,而在峡核小细胞部(Ipc)GABA阳性神经元仅位于核嘴内侧部.