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Endogenous histamine inhibits the development of morphine-induced conditioned place preference

Acta Pharmacologica Sinica 2007年第1期28卷 10-18页

作者： Ying-xia GONG~2 Min LV~(2,3) Yong-ping ZHU~2 Yuan-yuan ZHU~2 Er-qing WEI~2 Hong SHI~3 Qun-li ZENG~2 Zhong CHEN~(2,4)2 department of pharmacology and Neurobiology,School of Medicine,zhejiang University,hangzhou 310031,china 3 department of pharmacology,zhejiang academy of medical sciences,hangzhou 310031,china department of pharmacology and Neurobiology School of Medicine Zhejiang University Hangzhou China department of pharmacology Zhejiang Academy of Medical Sciences Hangzhou China

Aim:The conditioned place preference(CPP)paradigm was used to investigatethe effects of endogenous histamine on the processes leading to morphine-induced reward-seeking behavior in Sprague-Dawley ***:The modelof CPP was used to assess the rewarding effect of *** levels of histamine,glutamate,γ-aminobutyric acid(GABA),dopamine(DA)and 3,4-dihydroxyphenyl-acetic acid(DOPAC)in rat brains were measured with high-performance *** technique was used to observe themorphological changes of ***:Intraperitoneal injection of mor-phine(2,5 or 10 mg/kg)induced the development of CPP in a *** addition,morphine administrations(10 mg/kg)decreased the hista-mine content and reduced the number and size of histaminergic neurons in thetuberomammillary nucleus(TM),as well as markedly increasing the DOPAC/DAratios in the ventral tegmental area(VTA)and nucleus accumbens(NAc).Intra-peritoneal injection of histidine(50,100 or 200 mg/kg)dose-dependently inhibitedthe development of morphine-induced *** lesions of the TM,whichdecreased the histamine levels in the VTA and NAc,potentiated the developmentof CPP induced by morphine(1 mg/kg,a dose that produced no appreciable effectwhen given alone)and increased the DOPAC/DA ratios in the VTA and NAc,butdid not change the glutamate or GABA levels in these *** reversedthe effects of the TM ***:These results indicate that endog-enous histamine plays a role in inhibiting the development of morphine-inducedreward-seeking behavior,and the inhibition may involve the modulation of dopa-minergic activity.

关键词： conditioned place preference histamine morphine rat tuberomammillary nucleus

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Anti-inflammatory effect of amurensin H on asthma-like reaction induced by allergen in sensitized mice

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Acta Pharmacologica Sinica 2006年第6期27卷 735-740页

作者： Yi-tang LI~2 Chun-suo YAO~3 Jin-ye BAI~2 Man LIN~3 Gui-fang CHENG~(2,4)2 department of pharmacology,Institute of Materia Medica,Peking Union medical College and Chinese academy of medical sciences,Beijing 100050,china 3 department of Photochemistry,Institute of Materia Medica,Chinese academy of medical sciences and Peking Union medical College,Beijing 100050,china department of pharmacology Institute of Materia Medica Peking Union Medical College and Chinese Academy of Medical Sciences Beijing China department of Photochemistry Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Aim:To explore the anti-inflammatory effects of amurensin H on asthma-like reac-tion induced by allergen in sensitized ***:BALB/c mice were sensi-tized by ovalbumin(OVA,ip)on d 0 and d 14 and challenged with 1% OVA on d 18to *** developed airway eosinophilia,mucus hypersecretion,and elevationin cytokine *** were administered amurensin H orally at the doses of 49,70,or 100 mg/kg once every day from d 15 to the last *** lavagefluid(BALF)were collected at 24 h and 48 h after the last OVA *** tumor necrosis factor-α(TNF-α),interleukin 4(IL-4),interleukin 5(IL-5),andinterleukin 13(IL-13)in BALF were measured using ELISA *** counts of macrophages,lymphocytes,neutrophils and eosinophils were per-formed in 200 cells per slide(one slide per animal).Lung tissue sections of 6-μmthickness were stained with Mayer’s hematoxylin and eosin for assessment of cellinfiltration,mucus production,and tissue ***:Oral administrationof amurensin H significantly inhibited OVA-induced increases in total cell counts,eosinophil counts,and TNF-α,IL-4,IL-5 and IL-13 levels in *** addition,amuresin H dramatically decreased OVA-induced lung tissue damage and ***:Amurensin H may have therapeutic potential for thetreatment of allergic airway inflammation.

关键词： amurensin H asthma ovalbumin tumor necrosis factor-α Th2 cells cytokines

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Anticancer activity of sodium caffeate and its mechanism

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Acta Pharmacologica Sinica 2005年第10期26卷 1248-1252页

作者： Feng XU~(2,3,4), Sheng-hua ZHANG~3, Rong-guang SHAO~3, Yong-su ZHEN~3 ~2 department of pharmacology Zhujiang Hospital, Southern medical University Guangzhou 510280 ~3 department of Ontology Medicinal Biotechnology, Chinese academy of medical sciences and Peking Union medical College, Beijing 100050, china department of pharmacology Zhujiang Hospital Southern Medical University Guangzhou China department of Oncology Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Aim: To study the anticancer activity of sodium caffeate （SC）. Methods: A nucleoside transport assay was used to analyze the inhibitory effects of SC on nucleoside rescue. The MTT assay was used to measure cell proliferation. Flow cytometrywas used to measure the apoptosis of BEC-7402 induced by SC and the cell cycledistribution change. Western blotting analysis was employed to investigate Bcl2, caspase and Bax expression. Intracellular Ca2+and mitochondrial membranepotential were determined by flow cytometry. In vivo anti-tumor activity wasmeasured using a tumor transplantation model in mice. Results: SC inhibited thenucleoside transport of BEL-7402 cells with an IC50of 1.02 mg/mL. SC inhibitedtumor cell proliferation with an IC50between 100 μg/mL and 200μg/mL. SC induced BEL-7402 cell apoptosis in a time-and dose-dependent manner, which wasinduced by arresting cells in S phase. The in vivo study showed that tumorgrowth was inhibited in a dose-dependent manner. Activated caspase-3 and Baxexpression were up-regulated after treatment with SC, while Bcl-2 expression wasdown-regulated. Intracellular Ca2+was increased while mitochondrial membranepotential was decreased by SC. Conclusion: SC is a new anticancer agent withpromising potential.

关键词： caffeic acid anticancer activity cell division cell apoptosis cell cycle phytogenic antineoplastic agent flow cytometry Western blotting

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Chemopreventive effect of dimethyl dicarboxylate biphenyl on malignant transformation of WB-F344 rat liver epithelial cells

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Acta Pharmacologica Sinica 2005年第11期26卷 1339-1344页

作者： Hua SUN, Geng-tao LIU~2 ~2 department of pharmacology, Institute of Materia Medica, Peking Union medical College & Chinese academy of medical sciences, Beijing 100050, china department of pharmacology Institute of Materia Medica Peking Union Medical College & Chinese Academy of Medical Sciences Beijing China

Aim: To study the potential chemopreventive effect of dimethyl dicarboxylate biphenyl (DDB), an anti-hepatitis drug, on hepatocarcinogenesis in vitro. Methods: The anti-carcinogenesis effect of DDB was assessed on a two-stage chemical oncogenesis model induced by 3-methylcholanthrene and 12-0-tetradecanoyl phorbol 13-acetate (TPA) with WB-F344 rat liver epithelial cells (WB-F344 cells) in vitro. A soft-agar colony formation assay was used to determine the tumorigenic potential of the transformed WB-F344 cells. The gap junctional intercellular communication (GJIC) was detected using the scrape loading/ dye transfer technique. Results: DDB at 1 μmol/L, 2 μmol/L, and 4 μmol/L significantly prevented the malignant transformation of WB-F344 cells induced by 3-methylcholanthrene and TPA. The average number of transformed foci decreased dramatically by 10.0%, 37.2%, and 47.4%, respectively. In soft agar, a remarkable decrease in colony numbers was observed in transformed cells treated with 2 μmol/L and 4 μmol/L DDB. DDB at 1 μmol/L, 2 μmol/L, and 4 μmol/L inhibited the downregulation of GJIC induced by TPA in a dose-dependent manner. The GJIC recovered to 25.6%, 34.6%, and 44.9%, respectively, of the control WB-F344 cells by DDB. Conclusion: DDB has a potential chemopreventive effect on hepatocarcinogenesis induced by carcinogens in vitro.

关键词： dimethyl dicarboxylate biphenyl liver neoplasm: cell transformation chemoprevention epithelial cell gap junctions

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Protective effects of compound FLZ onβ-amyloid peptide-(25-35)-induced mouse hippocampal injury and learning and memory impairment

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Acta Pharmacologica Sinica 2006年第6期27卷 651-658页

作者： Fang FANG Geng-tao LIU~2 department of pharmacology,Institute of Materia Medica,Peking Union medical College and Chinese academy of medical sciences,Beijing 100050.china department of pharmacology Institute of Materia Medica Peking Union Medical College and Chinese Academy of Medical Sciences Beijing China

Aim:To study the protective effects of compound FLZ,a novel synthetic ana-logue of natural squamosamide,on learning and memory impairment and lesionsof the hippocampus caused by icv injection of β-amyloid25-35(Aβ25-35)in ***:Mice were icv injected with the Aβ25-35(15 nmol/mouse),and thentreated with oral administration of 75 mg/kg or 150 mg/kg of FLZ once daily for 16consecutive *** impairment of learning and memory in mice were testedusing step-down test and Morris water maze *** content of malondialdehyde(MDA)and the expressions of acetylcholinesterase(ACHE),Bax,and Bcl-2 in theCA1 region of the mouse hippocampus were measured by biochemical and immu-nohistochemical analysis,*** pathological damages of hippocam-pus were observed using a ***:FLZ(75 mg/kg,150 mg/kg)significantly attenuated Aβ25-35-induced impairment of learning and memory in thestep-down test and Morris water maze *** also reduced pathological dam-ages to the hippocampus induced by Aβ25-35Furthermore,FLZ prevented theincrease of AChE and Bax,and the decrease of Bcl-2 immunoreactive cells in theCA1 region of the hippocampus,and reduced the increase of MDA content in thehippocampus in mice injected with Aβ***:FLZ has protective ac-tion against the impairment of learning and memory and pathological damage tothe hippocampus induced by icv injection of Aβ25-35in mice.

关键词： FLZ Aβ25-35 intracerebroventricular injection hippocampus acetylcholinesterase Bax Bcl-2 malondialdehyde

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Detection and quantitation of PS20, a phosphorothioate oligodeoxynucleotides in monkey plasma

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Acta Pharmacologica Sinica 2004年第6期25卷 99-104页

作者： Ming-mei SHANG, Hai-feng SONG2, Xiu-wen LIU, Zhong-ming TANG department of pharmacology and Toxicology, the Institute of Radiation Medicine, academy of Military medical sciences, Beijing 100850, china department of pharmacology and Toxicology the Institute of Radiation Medicine Academy of Military Medical Sciences 北京 100850

AIM: To establish the method for quantitation of the phosphorothioate oligodeoxynucleotides (S-ODNs) in plasma. METHODS: Two solid-phase extraction columns combined with a strong anion-exchange column were utilized to remove proteins and lipids in plasma, and the salts were removed by a reverse-phase column followed by dialysis with a 2500 Da-cutoff membrane. The concentration of the tested S-ODNs, PS20, and its metabolites extracted from the plasma were determined by the method of non-gel sieving capillary electrophoresis (NGCE) with diode array detection in the presence of internal standard (IS). RESULTS: The method was with good base number specificity. Relative standard deviation % of both intra and inter assay were all less than 10 %, and the total mean recovery was about 91 %. The methodology was successfully used to determine the PK behavior of an anti-tumor antisense S-ODNs in monkeys and identify the metabolites with single base difference. CONCLUSION: The combined method of solid-phase extraction and NGCE could be used to study the pharmacokinetics of S-ODNs, and the main parameters of the methodology met the requirement of PK study.

关键词： antisense oligodeoxyribonucleotides thionucleotides rhesus monkey plasma solid-phase extraction capillary electrophoresis non-gel sieving internal standard

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Phosphorylated heat shock protein 27 is involved in enhanced heart tolerance to ischemia in short-term type 1 diabetic rats

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Acta Pharmacologica Sinica 2005年第7期26卷 806-812页

作者： Hong CHEN~(2,4,5) Xing-jun WU~2 Xi-yuan LU~3 Liang ZHU~2 Li-ping WANG~2 Huang-tian YANG~3 Hong-zhuan CHEN~(2,6) Wenjun YUAN~(4,6) 2 department of pharmacology,Shanghai Second medical University,Shanghai 200025 3 Laboratory of Molecular Cardiology,Health Science Center,Shanghai Second medical University,Shanghai Institute for Biological sciences,Chinese academy of sciences,Shanghai 200025 4 department of Physiology,Second Military medical University,Shanghai 200433,china 5 Now in department of pharmacology at Shanghai Second medical University,Shanghai 200025,china. department of pharmacology Shanghai Second Medical University Shanghai China department of Physiology Second Military Medical University Shanghai China Laboratory of Molecular Cardiology Health Science Center Shanghai Second Medical University Shanghai Institute for Biological Sciences Chinese Academy of Sciences Shanghai China

Aim:To examine the tolerance of type 1 diabetic hearts to ischemia and *** contents of 27-kDa and 70-kDa heat shock proteins（hsp）aswell as phosphorylated hsp27 were also ***:Hearts from hyper-glycemic rats 3 weeks after streptozocin injection and age-matched normal ratswere subjected to ischemia and reperfusion in *** function and electro-cardiogram were recorded throughout *** heat shock pro-teins were detected with Western ***:Despite depressed systolic func-tion at the baseline,diabetic hearts exhibited considerable enhancement in post-ischemic heart function,manifested by an increase in the maximal rate of leftventricular pressure rise and fall(post-ischemic dp/dtmaxand dp/dtminwere 560±117and-313±68 mmHg/s in control,n=7,1249±57 and-1204±36 mmHg/s in diabetes,n=10,P3 vs 7.2±2.1 min in control,P<0.01）.Theincreased heart resistance to ischemia in diabetes was associated with hypergly-cemia and accompanied by enhanced expression of myocardial phosphorylatedhsp27 with normal aortic vessel *** was abrogated bymetabolic correction with insulin and accompanied by phospho-hsp27 ***:Heart resistance to ischemia is increased in type 1 diabetes,andhyperglycemia may present a mild yet stressful stimulus leading to upregulationof endogenous stress protein,which may play a potential role in cardioprotectionand compensate for detrimental effects of hyperglycemia in diabetes.

关键词： type 1 diabetes mellitus ischemia reperfusion heart heat shock proteins

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Insulin-sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative in vitro

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Acta Pharmacologica Sinica 2007年第3期28卷 417-422页

作者： Hao-shu WU~(2,4) Juan-hong YU~(3,4) Ying-yin LI~2 Yu-she YANG~3 Qiao-jun HE~2 Yi-jia LOU~(2,5) Ru-yun JI~3 ~2department of pharmacology and Toxicology,College of Pharmaceutical sciences,zhejiang University,hangzhou 310058,china ~3State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institutes for Biological sciences,Graduate School of the Chinese academy of sciences,Shanghai 201203,china department of pharmacology and Toxicology College of Pharmaceutical Sciences Zhejiang University Hangzhou China department of State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Graduate School of the Chinese Academy of Sciences Shanghai China

Aim:To examine the insulin sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative YY20 in insulin-sensitive cell ***:Theperoxisome proliferator-activated receptor γ（PPARγ）agonist bioactivities of YY20were detected by a preadipocyte differentiation ***-PCR and Westernblotting analysis were used to detect the expression of the target gene or *** effects of YY20 on insulin-mediated glucose consumption were determined inthe HepG2 human hepatocellular carcinoma ***:YY20 could enhancethe differentiation of preadipocytes to adipocytes and upregulate the gene ex-pression of PPARγ2,as well as the protein expression of insulin receptor sub-strate-1（IRS-1）,glucose transporter-4（GLUT4）,and adiponectin（ACRP30）.Theeffects on GLUT4 and ACRP30 could be reversed by the PPARγ inhibitor ***,YY20 efficiently reduced glucose consumptions in HepG2 cells after24 h culture,and the effects were related to insulin and YY20 ***:YY20,a potential insulin-sensitizing agent like rosiglitazone,couldenhance glucose consumption in HepG2 cells in a concentration-and insulin-dependent *** may improve the insulin resistance associated with type 2diabetes.

关键词： YY20 peroxisome proliferator-activated receptor y insulin sensitivity glucose consumption

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Opioid receptor antagonists increase [Ca2+]i in rat arterial smooth muscle cells in hemorrhagic shock

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Acta Pharmacologica Sinica 2004年第3期25卷 141-146页

作者： Li KAI,Zhong-feng WANG2,Yu-liang SHI2,3,Liang-ming LIU,De-yao HU Institute of Surgery,department of pharmacology,Third Military medical University,Chongqing 400042 Key Laboratory of 2 Neurobiology,Shanghai Institutes for Biological sciences,Chinese academy of sciences,Shanghai 200031,china Institute of Surgery Department of Pharmacology Third Military Medical University 重庆 400042 中科院上海生命科学院 Key Laboratory of Neurobiology CAS 上海 200031

AIM: To examine the effects of opioid receptor antagonists and norepinephrine on intracellular free Ca2+ concentra- tion ([Ca2+]i) in mesenteric arterial (MA) smooth muscle cells (SMC) isolated from normal and hemorrhagic shocked rats in the vascular hyporesponse stage. METHODS: The rat model of hemorrhagic shock was made by withdrawing blood to decrease the artery mean blood pressure to 3.73-4.26 kPa and keeping at the level for 3 h. [Ca2+]i of vascular smooth muscle cells (VSMC) were detected by the laser scan confocal microscopy. RESULTS: In the hyporesponse VMSC of rats in hemorrhagic shock, selective δ-, κ-, and μ-opioid receptor antagonists (naltrindole, nor-binaltorphimine, and β-funaltrexamine, 100 nmol/L) as well as norepinephrine 5 μmol/L significantly increased [Ca2+]i by 47 %±13 %, 37 %±14 %, 33 %±10 %, and 54 %±17 %, respectively, although their effects were lower than those in the normal rat cells (the increased values were 148 %±54 %, 130 %±44 %, 63 %±17 % and 110 %±38 %, respectively); and the norepinephrine-induced increase in [Ca2+]i was further augmented by three δ-, κ-, and μ-opioid receptor antagonists (50 nmol/L, respectively) application (from 52 %±16 % to 99 %±29 %, 146 %±54 % and 137 %±47 %, respectively). CONCLUSION: The disorder of [Ca2+]i regulation induced by hemorrhagic shock was mediated by opioid receptor and α-adrenoceptor, which may be partly responsible for the vascular hyporesponse, and the opioid receptor antagonists improved the response of resistance arteries to vascu- lar stimulants in decompensatory stage of hemorrhagic shock.

关键词： hemorrhagic shock vascular smooth muscle opioid receptors calcium

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Beneficial effects of melatonin in experimental models of Alzheimer disease

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Acta Pharmacologica Sinica 2006年第2期27卷 129-139页

作者： Yong CHENG~2 Zheng FENG~3 Qing-zhu ZHANG~4 Jun-tian ZHANG~(2.5) ~2department of pharmacology,Institute of Materia Medica,Chinese academy of medical sciences and Peking Union medical College,Beijing 100050,china:~3department of Anesthesiology,University of California,San Diego,and Veterans Affairs medical Center,3350 La Jolla Village Drive,San Diego,CA 92161,USA:~4department of pharmacology,College of Pharmacy,Shandong University,Jinan 250012,china department of pharmacology Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China department of Anesthesiology University of California San Diego Veterans Affairs medical Center San Diego USA department of pharmacology College of Pharmacy Shandong University Jinan China

Alzheimer’s disease(AD),a progressive degenerative disorder,is characterizedby the presence of amyloid deposits,neurofibrillary tangles and neuron *** evidence indicates that antioxidants could be useful either for the pre-vention or treatment of *** has been shown that melatonin is a potent antioxi-dant and free radical ***,melatonin stimulates severalantioxidative enzymes and improves mitochondrial energy *** find-ings led us to study amyloid precursor protein transgenic mice,ovariectomizedrats,and pheochromocytoma and astroglioma cell lines,to observe whether mela-tonin had any effect on Alzheimer’s symptoms or pathological *** foundthat melatonin had many beneficial effects in experimental models of AD,includ-ing improvement of cognitive function,anti-oxidative injury,anti-apoptosis,inhi-bition of β-amyloid(Aβ)deposition and Aβ fiber *** groups haveshown that melatonin has an inhibitory effect on tau protein *** actions may potentially slow down or stop the progression of dementia.

关键词： melatonin Alzheimer disease beta-amyloid protein calcium overload APP transgenic mice ovariectomized rats tau protein hyperphosphorylation

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