大鼠电惊厥后人生长抑素受体的变化

目的 观察大鼠电惊厥后脑内生长抑素受体的变化。方法 应用受体结合放射自显影术、计算机显微图象处理技术、计算机显微图象处理技术观测。结果 正常大鼠大脑皮层、杏仁核、新纹状体、伏膈核、海马ＣＡ区、齿状回、嗅球、弓状核、下丘脑室周区、下丘脑腹内侧核、视前区内侧区、中央灰质、黑质等脑区内有＾１２５Ｉ－Ｔｙｒ＾１１－ＳＳ２８特异性结合；电惊厥后，大鼠颞叶听皮质、梨状皮质、内嗅皮质、杏二内侧核、海马ＣＡ区、齿     

用放射自显影术研究人参总皂甙对大鼠海马NMDA受体的影响

采用〔３Ｈ〕ＴＣＰ放射配基作海马ＮＭＤＡ受体的自显影，研究人参总皂甙在海马齿状回颗粒细胞层诱发ＬＴＰ效应和促进大鼠记忆保持能力时，海马内此受体的变化。给人参总皂甙的大鼠海马ＣＡ１、ＣＡ３和ＤＧ（ｄｅｎｔａｔｅｇｙｒｕｓ齿状回）的ＮＭＤＡ受体银粒数较给生理盐水大鼠的平均分别增多４２．８４％±２．４％，３８．５７％±３．１３％，３５．８１％±１．４６％（Ｐ＜０．０５、Ｐ＜０．０１），表明人参总皂甙在诱发海马ＬＴＰ和促进大鼠记忆行为时，可增加海马的ＮＭＤＡ受体数目和活性。     

4—16周龄高血压大鼠脑与脊髓苯环利定受体的变化(英文)

目的:研究高血压大鼠(SHR)脑和胸髓中苯环利定受体密度变化与高血压发生的关系.方法:4,8,12,16周大鼠中枢中[~3H]Phe标记的苯环利定受体密度用放射自显影法检测.结果:高血压稳定期(12,16周),SHR海马和胸髓背角中苯环利定受体明显少于非高血压大鼠(WKY);而血压升高前,4周的SHR则相反;8周血压开始上升时,SHR海马苯环利定受体增加,而在背角无差别.结论:苯环利定受体可能参与了SHR的发病过程.     

氯硝西泮抗惊厥作用耐受及停药后大鼠脑内NMDA受体放射自显影观察

氯硝西泮抗惊厥作用耐受及停药后大鼠脑内ＮＭＤＡ受体放射自显影观察廖建湘王丽左启华（北京医科大学第一医院儿科１０００３４）氯硝西泮是一种常用的抗癫痫药，但容易诱发耐受，而耐受后撤药又会导致撤药症状，从而限制其应用［１］。癫痫点燃动物模型脑组织及手术获...     

肝硬变门脉高压症大鼠和病人肝组织中H_1和H_2受体的变化

目的 了解H_1和H_2受体在肝硬变门静脉高压症大鼠和病人肝组织中的变化。方法 应用~3H-吡拉明和~3H-甲氰咪胍对四氯化碳诱导的10只大鼠肝硬变模型和8例乙型肝炎后肝硬变病人的肝组织进行光学放射自显影研究。结果 肝组织结构的H_1、H_2受体密度(每1000μm~2银粒计数)对照组/肝硬变大鼠分别为,H_1受体:肝细胞346.5±31.8/116.9±17.7,肝静脉276.9±17.6/27.1±4.6,肝动脉31.4±6.9/12.4±3.1,肝门静脉24.7±10.7/15.8±3.8;H_2受体:肝细胞288.9±21.2/168.0±23.7,肝动脉234.6±8.7/153.7±25.2,肝门静脉229.8±28.3/148.3±18.0,肝静脉261.3±35.8/141.0±18.3。对照组/肝硬变病人H_1受体:肝细胞68.7±8.7/63.1±5.5,肝动脉40.6±7.5/35.5±4.7,肝门静脉38.8±5.2/34.4±6.8,肝静脉35.6±8.2/34.7±5.0;H_2受体:肝细胞511.9±37.6/168.4±22.6,肝动脉175.4±26.1/55.6±7.1,肝门静脉166.4±17.7/52.0±5.4,肝静脉313.0±52.4/238.8±40.7。结论 大鼠以H_1受体占优势,人以H_2受体为主;肝硬变大鼠及病人肝组织结构上的H_1、H_2受体低于对照组。     

[^3H]二氢埃托啡在大鼠脑分布的定理放射自显影

本用体外定量受体放射自显影分析观察了［＾３Ｈ］二氢埃托啡在大鼠脑中定位分布和结合特点。结果表明，［＾３Ｈ］ＤＨＥ特异结合较高的部位主要为纹状体，伏隔核，大脑皮质Ⅰ层和Ⅱ层，丘脑，缰核，杏仁核，脚间核和蓝斑。     

兔小脑μ阿片受体的特性及其分布

应用放射配体结合试验和放射自显影研究了［＾３Ｈ］羟甲芬太尼（［＾３Ｈ］ＯＭＦ），［＾３Ｈ］埃托啡（［＾３Ｈ］Ｅｔｏ），［＾３Ｈ］Ｕ６９５９３和［＾３Ｈ］ＤＰＤＰＥ与兔小脑的结合特性。［＾３］ＯＭＦ和［＾３Ｈ］Ｅｔｏ与兔小脑有一呈饱和性的单位点的结合，它们的Ｋｄ分别为２．２±１．３和１．０±０．４ｎｍｏｌ·Ｌ＾－１，Ｂｍａｘ分别为６９±１３和１６±６ｆｍｏｌ／ｍｇ蛋白。［＾３Ｈ］Ｕ６９５９３和［＾３     

卡马西平对青霉素点燃惊厥大鼠脑内GABA_A受体mRNA表达的作用

目的研究两种剂量卡马西平对青霉素慢性点燃大鼠的抗惊厥作用及对脑内GABAA受体mRNA表达的影响,从基因水平探讨卡马西平抗惊厥的作用机制。方法采用腹腔注射(ip)青霉素(3×106U.kg-1.d-1)慢性点燃大鼠惊厥模型,两种剂量卡马西平(50,100mg.kg-1×13d)ig给药,以痫性发作潜伏期和Racine惊厥行为分级标准为判定药效指标,观察卡马西平的抗惊厥作用。运用RT-PCR技术测定大鼠脑内GABAA受体mRNA表达量,分析卡马西平抗惊厥作用的新机制。结果两种剂量卡马西平ig给药后,均可使青霉素慢性点燃大鼠痫性发作的潜伏期延长,与模型对照组相比差异有统计学意义(P<0.01),同时使惊厥大鼠的发作程度均较模型对照组减轻。青霉素慢性点燃大鼠脑内GABAA受体mRNA表达减少,与正常对照组比较,差异有统计学意义(P<0.01);两种剂量卡马西平预防性干预组的GABAA受体mRNA表达量分别与模型对照组相比,差异均无显著性。结论两种剂量卡马西平对青霉素慢性点燃的惊厥发作均有明显的对抗作用,但抗惊厥机制与GABAA受体的基因表达无关。     

阿片受体在自发性高血压大鼠和正常大鼠中的不同分布(英文)

目的:比较16周自发性高血压大鼠(SHR)和对照组Wistar-Kyoto(WKY)大鼠中枢神经系统中与血压调节有关的核团内阿片受体密度的变化.方法:用放射自显影方法,运用氚标依托啡作配基检测阿片受体的分布. 结果:在海马(P<0.01)、中央灰质、孤束核、胸髓(P<0.05)几处,SHR阿片受体密度较WKY大鼠低;而在杏仁核(P<0.01)、僵核(P<0.05)和下丘脑核群包括弓状核(P<0.01),SHR却有较高的阿片受体密度. 结论:不同分布的阿片受体与自发性高血压大鼠的血压有关.     

Changes in immunoreactive somatostatin in brain following lidocaine-induced kindling in rat

The kindling phenomenon has become a useful model for studying epileptogenesis. The present authors have previously reported increased levels of immunoreactive somatostatin (IR-SRIF) in various regions of the brain of electrically-amygdaloid kindled (EAK) rats. In this study, an examination was made of immunoreactive somatostatin in pharmacologically-kindled (PK) rats. Sixteen male Sprague-Dawley rats were injected intraperitoneally (i.p.) with a subthreshold dose of lidocaine (60 mg/kg), once daily. Once the kindling phenomenon was established, kindled rats (7), non-kindled rats (9) and controls (6) were sacrificed by microwave irradiation. Another group of 5 rats was injected with a single suprathreshold dose of lidocaine (110 mg/kg) and killed 10 min after the resultant seizure. Various brain areas were removed and assayed for immunoreactive somatostatin in kindled rats. Immunoreactive somatostatin was significantly greater than in controls in the amygdala (56%; P less than 0.02), entorhinal + piriform cortex (50%; P less than 0.05) and hypothalamus (29%; P less than 0.02). In non-kindled rats, immunoreactive somatostatin increased only in the amygdala (58%; P less than 0.02). No difference was found in the immunoreactive somatostatin content of rats injected with an suprathreshold dose of lidocaine compared to controls. The alteration of immunoreactive somatostatin, in both lidocaine-kindled and electrically-amygdaloid kindled rats suggests a possible role of this neuropeptide in kindling.     

The antiproliferative effects of somatostatin receptor subtype 2 in breast cancer cells

Aim： Somatostatin receptor subtype 2 （SSTR2） is the principal mediator of somatostatin＇s （SST） antiproliferative effects on normal and cancer cells. Therefore, we investigated whether the enhanced expression of SSTR2 could inhibit the proliferation of tumor cells, and, if so, the mechanisms that might be involved.
Methods： SSTR2 expression levels were determined by qRToPCR in several tumor cell lines. Then, a plasmid plRES2-EGFP-SSTR2 （pSlG） was constructed and stably transfected into MCF-7 cells （MCF-7/pSIG）. After SSTR2 overexpression was identified by qRT-PCR, immunofluorescence staining and a receptor binding assay, the MCF-7/pSIG cells were analyzed by PI staining for apoptosis and cell cycle arrest was tested by flow cytometry for epidermal growth factor receptor （EGFR） expression. The EGF-stimulated proliferation of MCF-7 cells was assayed by MTT.
Results： The human breast cancer cell line MCF-7 expresses a lower level of SSTR2, thereby partly accounting for the decreased response to SST. The overexpression of SSTR2 in MCF-7 cells resulted in apoptosis, cytostasis and G1/S cell cycle arrest. Furthermore the expression of EGFR, together with EGF-stimulated proliferation, was markedly decreased in the MCF-7/pSlG cells.
Conclusion： Enhanced SSTR2 expression played an antiproliferative role in MCF-7 cells through inducing apoptosis and G1/S cell cycle arrest, and also by decreasing EGFR expression, thereby counteracting the growth-stimulating effect of EGF. Our data seem to indicate that developing a new therapeutic agent capable of upregulating SSTR expression could potentially be a way to block tumor progression.     

Allosteric modulation of the GABA(A) receptor in rat hypothalamus by somatostatin is altered by stress

1. This autoradiographic study was conducted to investigate somatostatin modulation of GABA(A) receptor binding in hypothalamic structures of immobilization-stressed rats. 2. GABA(A) receptor binding was labelled with [35S]-t- butylbicyclophosphorothionate (TBPS), which binds in or near the chloride channel. 3. Several structures of the rat hypothalamus (i.e. the peri- and paraventricular nuclei) display an increase in [35S]-TBPS binding as well as an alteration of the modulatory effect of somatostatin on the GABA(A) receptor complex under stress. Furthermore, these results demonstrate for the first time that somatostatin is particularly effective in modifying [35S]-TBPS binding to the GABA(A) receptor in rat hypothalamus.     

Involvement of somatostatin receptor subtypes in membrane ion channel modification by somatostatin in pituitary somatotropes

1. Growth hormone (GH) secretion from pituitary somatotropes is mainly regulated by two hypothalamic hormones, GH-releasing hormone (GHRH) and somatotrophin releasing inhibitory factor (SRIF). 2. Somatotrophin releasing inhibitory factor inhibits GH secretion via activation of specific membrane receptors, somatostatin receptors (SSTRs) and signalling transduction systems in somatotropes. 3. Five subtypes of SSTRs, namely SSTR1, 2, 3, 4 and 5, have been identified, with the SSTR2 subtype divided into SSTR2A and SSTR2B. All SSTRs are G-protein-coupled receptors. 4. Voltage-gated Ca(2+) and K(+) channels on the somatotrope membrane play an important role in regulating GH secretion and SRIF modifies both channels to reduce intracellular free Ca(2+) concentration and GH secretion. 5. Using specific SSTR subtype-specific agonists, it has been found that reduction in Ca(2+) currents by SRIF is mediated by SSTR2 and an increase in K(+) currents is mediated by both SSTR2 and SSTR4 in rat somatotropes.     

Modulation Of [35S]-tert-butylbicyclophosphorothionate binding by somatostatin in rat hypothalamus

1. The present study was designed to assess the effect of the tetradecapeptide somatostatin on the GABA(A) receptor complex in the rat hypothalamus. 2. GABA(A) receptors were labelled with [35S]-tert-butylbicyclophosphorothionate (TBPS), which binds in or near the chloride channel, and binding as assessed by in vitro quantitative autoradiography using a computer-assisted image analysis system. 3. Somatostatin inhibited the binding of [35S]-TBPS to the convulsant site of the hypothalamic GABA(A) receptor complex of rat slide-mounted hypothalamic structures in a concentration-dependent manner with an affinity in the micromolar range (10(-6) to 3 x 10(-6) mol/L). Somatostatin appeared to mimic the effects of the neurosteroid 5alpha-pregnane-3alpha ol-one (5alpha3alphaP), GABA and picrotoxin on [35S]-TBPS binding in the rat hypothalamus in all structures examined. Furthermore, GABA or muscimol (a GABA(A) receptor agonist), when added to the incubation medium, enhanced the capacity of somatostatin to inhibit [35S]-TBPS binding, with an IC50 of 10(-7) mol/L. However, incubation with bicuculline (a GABA(A) receptor antagonist) led to the abolition of the inhibitory effect of somatostatin on [35S]-TBPS specific binding in rat hypothalamus. 4. The present results demonstrate the presence of a modulatory effect of somatostatin on the GABA(A) receptor complex in rat hypothalamic structures. Furthermore, the data suggest that somatostatin allosterically modifies [35S]-TBPS binding through a mechanism similar to that of GABA. Taken together, these results provide evidence for the presence of somatostatin- GABA interactions in rat hypothalamus.     

Distribution of GABAA and GABAB receptors in mammalian brain: Potential targets for drug development

GABA is the major inhibitory neurotransmitter in mammalian brain. GABA receptors and the metabolism of GABA are significant targets for new centrally acting drugs to treat neurological and behavioral disorders. The simple neutral amino acid is likely to subserve a neurotransmitter role at 25–50% of all synapses in the central nervous system. GABA's actions are mediated by two different receptors, GABA_A and GABA_B receptors. GABA_A receptors are ligand-gated chloride channels that are sensitive to the convulsant alkaloid bicuculline and modulated by benzodiazepines and barbiturates. GABA_B receptors affect calcium and potassium conductance through GTP binding proteins and are insensitive to bicuculline and sensitive to the agonist baclofen. Both receptors are widely distributed in cerebral cortex, hippocampus, basal ganglia, thalamus, cerebellum, and brainstem.     

生长抑素抑制大肠癌细胞增殖及机制的研究进展

生长抑素是一种广泛存在于中枢神经系统、胃肠道和胰腺组织内的,具有广泛抑制作用的胃肠激素。大量研究表明生长抑素及其类似物具有抗肿瘤活性,能抑制内分泌肿瘤的增殖,且表现出对许多实体肿瘤,尤其是消化系统肿瘤有抑制作用。本文将对近几年关于生长抑素及其类似物影响大肠癌细胞增殖机制的研究进展作一综述。     

The somatostatin receptor subtype 5 in neuroendocrine tumours

Importance of the field: In recent years, scientific work has been intensified to unravel new (patho-) physiological insights, particularly regarding the functional role of somatostatin (SRIF) receptor subtype 5 (sst) and the development of novel sst₅-targeted SRIF analogues, in order to broaden medical therapeutic opportunities in patients suffering from neuroendocrine diseases.

Areas covered in this review: The scope of this review is primarily focused upon recent insights in sst₅-receptor physiology, novel sst₅-targeted treatment options predominantly directed towards pituitary adenomas, and gastroenteropancreatic neuroendocrine tumours.

What the reader will gain: An understanding of the potential that novel sst₅-targeted SRIF analogues might have in the medical treatment of Cushing’s disease and acromegaly, as demonstrated by translational research, based on pathophysiological data combined with results from clinical trials.

Take home message: The role of targeting sst₅ in gastroenteropancreatic neuroendocrine tumours remains to be established. The sst₅ subtype might function as sst₂ modulator in terms of receptor internalization and desensitization, and seems less important compared with sst₂-preferring SRIF analogues in the regulation of human insulin secretion by the pancreas. Finally, absence of sst₅ in corticotroph adenomas could be related to tumour aggressiveness in Cushing’s disease.