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Stimulation by nizatidine,a histamine H_2-receptor antagonist,of duodenal HCO_3^-secretion in rats:relation to anti-cholinesterase activity 被引量:1
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作者 Koji Takeuchi Shoji Kawauchi +2 位作者 Hideo Araki Shigeru Ueki Osamu Furukawa 《World Journal of Gastroenterology》 SCIE CAS CSCD 2000年第5期651-658,共8页
AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secre... AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent. 展开更多
关键词 NIZATIDINE histamine h_2 receptor blockaders duodenal hCO_3^-secretion cholinesterase inhibitors RATS
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In vivo immunomodulatory profile of histamine receptors(H1,H2,H3 and H4):a comparative antagonists study
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作者 Trivendra Tripathi Mohammad Shahid +3 位作者 Haris M Khan Aijaz Ahmed Khan Mashiatullah Siddiqui Rahat Ali Khan 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2010年第6期465-470,共6页
Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each g... Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each group.GroupⅠremained non-immunized and received only vehicle(sterile distilled water,1 mL/kg×b.i.d.) intramuscularly.GroupⅡreceived vehicle (1 mL/kg×b.i.d.) while GroupsⅢ-Ⅶ(drugs-treated) received subcutaneous histamine (100μg/kg×b.i.d.),and intramuscular H1R-antagonist(pheniramine,10 mg/kg×b.i.d.), H2R-antagonist(ranitidine,10 mg/kg×b.i.d.),H3R-antagonist(iodophenpropit,1μg/kg×b.i.d.) and H4R-antagonist(JNJ 7777120,10μg/kg×b.i.d.),and GroupⅧDMSO(1 mL/kg×b.i.d.),respectively for 10 days(starting from day 1).They were subsequendy immunized with intravenous injection of sheep red blood cells(SRBC) at day 3.The estimation of serum Igs,IgM and IgG were done by ELISA,and observed at day 0(pre-immunization),and 7,14,21,28 and 58(post-immunization).Results:It was shown that histamine and HRs-antagonists could influence a detectable antibody response to SRBC as early as day 7-post-immunization(post-Ⅰ), which lasted until day 58 post-Ⅰ.The results were found statistically significant(P【0.05,). Conclusions:This study suggests that histamine receptors play important roles in modulation of antibody generation in which H1R,H2R and H4R have immunosuppressive roles and conversely, H3R playes an immune enhancing role.The findings of this study may have clinical significance and provide the baseline information for future study. 展开更多
关键词 histamine receptors IMMUNOMODULATION hUMORAL immune response h3R-antagonist h4R-antagonist
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Changes in hippocampal histamine receptors in rats after treatment with Trimeresurus albolabris venom
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作者 Qiyi He Min Deng Xiaodong Yu Hui Li Yixin Lin Xia Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第7期728-732,共5页
BACKGROUND: It has been demonstrated that histamine and its receptors in the hippocampus play an important role in memory and/or learning behaviors.OBJECTIVE: To investigate the expression levels of the histamine re... BACKGROUND: It has been demonstrated that histamine and its receptors in the hippocampus play an important role in memory and/or learning behaviors.OBJECTIVE: To investigate the expression levels of the histamine receptor gene and protein in the hippocampi of rats prior to and after administration of Trimeresurus albolabris venom using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot techniques. DESIGN, TIME AND SETTING: A controlled observation based on cellular protein level was performed in the College of Life Sciences, Chongqing Normal University between March 2005 and April 2007. MATERIALS: Eighty adult male Sprague-Dawley rats were provided by the Laboratory Animal Center of the Third Military Medical University of Chinese PLA. The lyophilized powder of Trimeresurus albolabris venom was collected from Jin-Hu-Shan in Chongqing, China. METHODS: Twenty rats were randomly and evenly divided into an experimental group and a control group The experimental group was subcutaneously injected with 0.65 mg/mL Trimeresurus albolabris venom, 0.5 mL for each rat. The control group was subcutaneously injected with an equal amount of 0.9% physiological saline. Prior to and after injection, rats from these two groups were placed in the Morris Water Maze for recording of path length and escape latency. The remaining 60 rats were randomly allocated to another experimental group (n = 50) and another control group (n = 10). Rats were correspondingly injected as described above. At different time points (0.1, 0.5, 1, 2, and 3 hours after injection), rats were decapitated and bilateral hippocampal tissues were dissociated (approximately 100 mg for each sample). Then, the acquired hippocampal tissue was immediately preserved at -70 ℃ for subsequent experiments. MAIN OUTCOME MEASURES: (1) The levels of histamine receptor (including H1R, H2R, and H3R) mRNA and protein in the hippocampi of rats were measured prior to and after injection of Trimeresurus albolabris venom using RT-PCR and Western Blot techniques. (2) Escape latency (namely, time to reach a platform) and path length were examined by Morris Water Maze testing. RESULTS: All 80 rats were included in the final analysis. In the experimental group, the level of mRNA for H3R receptor in rat hippocampi was just slightly changed, but the level of H3R receptor protein was significantly down-regulated compared with that in the control group (P 〈 0.05). Both mRNA and protein levels for H1R receptor were initially downregulated and then recovered to normal levels. Expression of H2R receptor mRNA was initially upregulated, then downregulated, and finally restored to the control level. The level of H2R receptor protein showed a tendency for downregulation. In the Morris Water Maze testing, escape latency and path length were significantly longer in the experimental group than in the control group (P 〈 0.05). CONCLUSION: Within three hours of injection with Trimeresurus albolabris venom, mRNA and protein levels of most histamine receptors in rat hippocampi were downregulated. Such changes possibly contribute to an impairment of memory and/or learning behaviors in rats following injection of Trimeresurus albolabris venom. 展开更多
关键词 Trimeresurus albolabris histamine receptor h1 h2 h3 SNAKEBITE snake venom
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Effects of splice sites on the intron retention in histamine H_3 receptors from rats and mice
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作者 Wenyong Ding Lin Lin +3 位作者 Feng Ren Hanfa Zou Ziyuan Duan Jianwu Dai 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2009年第8期475-482,共8页
In the alternative splicing, intron retention, of histamine H3 receptors in rats and mice, the short transcript isoforms that are excised alternatively spliced introns are easily detected in a very low level in rats a... In the alternative splicing, intron retention, of histamine H3 receptors in rats and mice, the short transcript isoforms that are excised alternatively spliced introns are easily detected in a very low level in rats and are undetectable in mice using the regular PCR protocol. The retained introns have common 5' splice site and different 3' splice sites. The detailed mechanism for the special alternative splicing remains largely unclear. In this study, we developed a minigene splicing system to recapitulate natural alternative splicing of the receptors and investigated the effects of 5' and 3' splice sites on intron retention in HeLa cells. Mutating weak 5' and 3' splice sites of the alternatively spliced introns toward the canonical consensus sequences promoted the splicing of the corresponding introns in rat and mouse minigenes. The effect of splice site strength was context-dependent and much more sigiaificant for the 3' splice site of the longer alternative intron than for the 3' splice site of the shorter alternative intron and the common 5' splice sites; it was also more significant in the rat minigene than in the mouse minigene. Mutating the 3' splice site of the longer alternative intron resulted in almost complete splicing of the intron and made the corresponding isoform to become the nearly exclusive transcript in the rat minigene. 展开更多
关键词 histamine h3 receptor h3R) altemative splicing intron retention splice site MINIGENE
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组胺H_3受体对心血管系统的调控作用 被引量:7
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作者 李明凯 罗晓星 《中国药理学通报》 CAS CSCD 北大核心 2002年第6期608-610,共3页
综述了组胺H3受体的细胞内信号转导途径 。
关键词 组胺h3受体 组胺 组胺h3受体激动剂 心血管系统 负反馈调控 信号转录
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组胺H_3受体对垂体瘤AtT-20细胞分泌ACTH的调节作用 被引量:3
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作者 谢建军 罗晓星 赵德化 《第四军医大学学报》 北大核心 2001年第7期584-586,共3页
目的 观察组胺受体激动剂对 At T- 2 0细胞分泌ACTH的影响 ,并探讨 G蛋白在组胺 H3受体信号转导机制中的作用 .方法 选用文献报道的高表达组胺 H3受体的垂体细胞瘤 At T- 2 0作为观察系统 ,用放免分析法测定给予组胺受体激动剂后各时... 目的 观察组胺受体激动剂对 At T- 2 0细胞分泌ACTH的影响 ,并探讨 G蛋白在组胺 H3受体信号转导机制中的作用 .方法 选用文献报道的高表达组胺 H3受体的垂体细胞瘤 At T- 2 0作为观察系统 ,用放免分析法测定给予组胺受体激动剂后各时间点细胞上清液中 ACTH分泌量的变化 ,并观察药物对细胞增殖的影响 .结果 组胺 H3受体激动剂R- (α) - Me HA(0 .1μmol· L- 1 )作用 8h能明显促进 ACTH的释放 ,释放量为 192 0 μg· L- 1 ,与同时间对照组 (780 μg·L- 1 )相比 ,明显增高 (P<0 .0 1) ;H1 和 H2 激动剂则无此作用 .且 R- (α) - Me HA引起 ACTH分泌的效应能被 H3受体特异性拮抗剂 thioperamide所拮抗 ,而 H1 受体和 H2 受体拮抗剂均不影响 R- (α) - Me HA的效应 .R- (α) - Me HA作用 8和 2 4h,对细胞增殖无明显影响 .用 G蛋白失活剂 NEM预先处理细胞后 ,取消了 R- (α) - Me HA增强 At T- 2 0细胞 ACTH分泌的效应 .结论 特异性激动组胺 H3受体后能引起兴奋 -分泌耦联过程 ,其信号转导过程中有 G蛋白的参与 . 展开更多
关键词 组胺h3受体 AtT-20细胞 垂体瘤 促肾上腺皮质激素 G蛋白
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哮喘豚鼠脑内组胺含量的变化及中枢组胺H_3受体的调节作用 被引量:8
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作者 董榕 张敏 +1 位作者 时斌 许诚 《现代医学》 2003年第3期154-156,共3页
目的 检测豚鼠哮喘急性发作时脑内组胺含量的变化 ,观察中枢组胺H3受体在哮喘未发作时对脑内组胺含量的影响。方法 哮喘急性发作组豚鼠给予腹腔注射卵蛋白致敏 ;阴性对照组豚鼠给予腹腔注射等量生理盐水 ;THIO组豚鼠在哮喘未发作期侧... 目的 检测豚鼠哮喘急性发作时脑内组胺含量的变化 ,观察中枢组胺H3受体在哮喘未发作时对脑内组胺含量的影响。方法 哮喘急性发作组豚鼠给予腹腔注射卵蛋白致敏 ;阴性对照组豚鼠给予腹腔注射等量生理盐水 ;THIO组豚鼠在哮喘未发作期侧脑室内注射H3受体拮抗剂thioperamide (2 0 μg) ;生理盐水组豚鼠在哮喘未发作期侧脑室内注射等量生理盐水。断头处死动物后 ,在冰台上迅速分离出下丘脑、大脑皮质和海马 ,称重 ,匀浆 ,荧光法测定组胺含量。结果 哮喘急性发作组 ,下丘脑和大脑皮质中的组胺含量高于阴性对照组 ,差异有显著意义 (P <0 0 1) ;海马内组胺含量差异无显著意义 (P >0 0 5 )。哮喘未发作期侧脑室注射thioperamide后 ,下丘脑和大脑皮质中的组胺含量均升高 ,与生理盐水组比较差异有显著意义 (P <0 0 5 ) ,海马内组胺含量无显著变化 (P >0 .0 5 )。结论 中枢组胺含量与哮喘发作有关 。 展开更多
关键词 哮喘 组胺 h3受体 病理生理学
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组胺H_3受体定位于心交感神经末梢突触前膜的进一步证明
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作者 罗晓星 禹更生 谭月华 《第四军医大学学报》 1995年第5期324-327,共4页
目的:观察[ ̄3H]组胺在心肌细胞粗制膜上的结合情况.方法:制备心肌细胞粗制膜,将膜制备与[ ̄3H]组胺在37℃下共同孵育30min,然后将孵育液经玻璃纤维膜减压抽滤.滤膜烘干后放入闪烁瓶中,记录放射活性.结果:选择... 目的:观察[ ̄3H]组胺在心肌细胞粗制膜上的结合情况.方法:制备心肌细胞粗制膜,将膜制备与[ ̄3H]组胺在37℃下共同孵育30min,然后将孵育液经玻璃纤维膜减压抽滤.滤膜烘干后放入闪烁瓶中,记录放射活性.结果:选择性H-3受体激动剂α-甲基组胺(α-MeHA,1μmol/L)可竞争性抑制[ ̄3H]组胺在心肌膜制备上的特异性结合,[ ̄3H]组胺(0.5和1 nmol/L)特异性结合量减少至对照值的64.1±11.1%和60.51±4.1%。6-羟基多巴胺(6-OHDA)化学切割交感神经后,可以使[ ̄3H]组胺与膜受体的结合量减少至对照值的77.3±6.9%和80.1±6.9%.在化学去交感神经的膜制备中,α-MeHA仅轻度降低组胺与膜受体的特异性结合量.结论:化学法切除交感神经后,丢失了一部分与[ ̄3H]组胺结合的受体蛋白,这部分定位于交感神经末梢的组胺受体,可以被α-MeHA竞争性结合,属于组胺H-3受体. 展开更多
关键词 心肌 交感神经末梢 突触 组胺h3受体 受体
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Imetit Dihydrobromide and Thioperamide Medication in Cough Hypersensitivity Model—The Role of H3 Receptors
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作者 Tomas Buday Eva Kovacova +3 位作者 Silvia Gavliakova Natalia Kavalcikova-Bogdanova Martina Antosova Jana Plevkova 《Open Journal of Molecular and Integrative Physiology》 2016年第1期1-9,共9页
Chronic cough is a troublesome problem and it is frequently associated with diseases such as gastroesophageal reflux, asthma and upper airway diseases—so called diagnostic triade. The magnitude and severity of cough ... Chronic cough is a troublesome problem and it is frequently associated with diseases such as gastroesophageal reflux, asthma and upper airway diseases—so called diagnostic triade. The magnitude and severity of cough is strongly associated with the ongoing nasal inflammation in subjects with rhinosinusitis and treatment of nasal inflammation leads to the down regulation of pathologically up-regulated cough. Histamine plays a key role in the inflammation of the upper airways of different aetiologies;therefore histamine receptors seem to be promising targets. The aim of our study was to ascertain the effect of H<sub>3</sub>R agonist imetit and H<sub>3</sub>R antagonist thioperamide on cough and symptoms of allergic rhinitis (AR) in an animal model of upper airway cough syndrome in ovalbumin sensitized guinea pigs. OVA sensitized guinea pigs (n = 10) were repeatedly challenged with i.n. allergen-OVA to induce allergic rhinitis and to enhance cough reflex according to the validated model of experimental allergic rhinitis. Animals were pre-treated by i.p. administration of imetit (1 mg/kg and 2 mg/kg of body weight) and thioperamide 30 min. prior i.n. OVA administration. Rhinitis evaluation was based on the occurrence of typical symptoms. The effect on cough was assessed from the response to inhalation of citric acid (0.4 M, 10 min), final cough count and cough latency were analysed from the airflow traces, cough motor pattern and the cough sound. AR up-regulated the cough response from 9 ± 2 to 16 ± 1 cough per provocation, med ± IQR, p < 0.05 and shortened cough latency. Imetit (1 mg/kg) suppressed nasal symptoms and decreased number of cough from 16 ± 1 to 12 ± 1;however the data did not reach significance. Imetit (2 mg/kg) significantly suppressed the nasal symptoms, and number of coughs from 16 ± 1 to 6 ± 2, med ± IQR, p < 0.05. Thioperamide (5 mg/kg of body weight) did not have expected effects on tested parameters. H3R agonist imetit, unlike H3R antagonist thioperamide has antitussive potential and ability to suppress nasal symptoms in animal model of allergic rhinitis. 展开更多
关键词 Chronic Cough Allergic Rhinitis histamine ANTITUSSIVE Imetit ThIOPERAMIDE h3 Receptor
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Gastro-protective action of lafutidine mediated by capsaicin-sensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins 被引量:6
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作者 Kazuhiro Fukushima Yoko Aoi +1 位作者 Shinichi Kato Koji Takeuchi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第19期3031-3037,共7页
AIM: Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons (CSN). We compared the effect between lafutidine and capsaicin, with respect to... AIM: Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons (CSN). We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins (PG), nitric oxide (NO) and the afferent neurons, including transient receptor potential vanilloid subtype 1 (TRPV1). METHODS: Male SD rats and C57BL/6 mice, both wildtype and prostacyclin IP receptor knockout animals, were used after 18 h of fasting. Gastric lesions were induced by the po administration of HCl/ethanol (60% in 150 mmol/L HCl) in a volume of 1 mL for rats or 0.3 mL for mice. RESULTS: Both lafutidine and capsaicin (1-10 mg/kg, po) afforded dose-dependent protection against HCI/ ethanol in rats and mice. The effects were attenuated by both the ablation of CSN and pretreatment with NG-nitro- L-arginine methyl ester, yet only the effect of capsaicin was mitigated by prior administration of capsazepine, the TRPV1 antagonist, as well as indomethacin. Lafutidine protected the stomach against HCl/ethanol in IP receptor knockout mice, similar to wild-type animals, while capsaicin failed to afford protection in the animals lacking IP receptors. Neither of these agents affected the mucosal PGE2 or 6-keto PGF1α contents in rat stomachs. Capsaicin evoked an increase in [Ca^2+]i in rat TRPV1-transfected HEK293 cells while lafutidine did not. CONCLUSION: These results suggest that although both lafutidine and capsaicin exhibit gastro-protective action mediated by CSN, the mode of their effects differs regarding the dependency on endogenous PGs/IP receptors and TRPV1. It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1. 展开更多
关键词 LAFUTIDINE A histamine h2-receptor antagonist Gastric protection Prostaglandin Capsaicin-sensirive afferent neuron TRPVt
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脑内组胺对戊四唑慢性癫痫形成过程的作用机制 被引量:4
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作者 张力三 沈海清 +3 位作者 金春雷 胡薇薇 赵孟辉 陈忠 《浙江大学学报(医学版)》 CAS CSCD 2004年第3期201-204,共4页
目的 :探讨组胺对戊四唑诱发慢性癫痫形成的作用机制。方法 :大鼠隔日腹腔注射亚惊厥剂量的戊四唑( 35 mg/ kg)诱发化学点燃癫痫。观察每次戊四唑注射后 30 min内的癫痫发作行为变化。结果 :腹腔内注射组氨酸或侧脑室内注射 clobenpropi... 目的 :探讨组胺对戊四唑诱发慢性癫痫形成的作用机制。方法 :大鼠隔日腹腔注射亚惊厥剂量的戊四唑( 35 mg/ kg)诱发化学点燃癫痫。观察每次戊四唑注射后 30 min内的癫痫发作行为变化。结果 :腹腔内注射组氨酸或侧脑室内注射 clobenpropit都能剂量依赖性地延缓癫痫的形成 ,表现为延长肌性痉挛、阵挛性癫痫全身性发作的反应潜伏时间及抑制癫痫发作的级别。 H3 受体激动剂 immepip和组氨酸脱羧酶抑制剂α-氟甲基组氨酸剂量依赖性地抑制 clobenpropit的抗癫痫作用。结论 :脑内组胺在对抗阵挛性癫痫发作中起较重要的作用 ,其作用主要与 展开更多
关键词 癫痫/化学诱导 组氨酸/药理学 h3受体 组胺 戊四唑
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组胺H_3受体介导抑制豚鼠心交感神经释放去甲肾上腺素的直接依据
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作者 罗晓星 文爱东 +1 位作者 郭治安 谭月华 《中国药理学报》 CSCD 1996年第5期425-428,共4页
组胺H3受体介导抑制豚鼠心交感神经释放去甲肾上腺素的直接依据罗晓星,文爱东1,郭治安2,谭月华(第四军医大学药理教研室,1西京医院临床药理室;2西北大学化学系,西安710032,中国)关键词心房;电刺激;甲基组胺;组... 组胺H3受体介导抑制豚鼠心交感神经释放去甲肾上腺素的直接依据罗晓星,文爱东1,郭治安2,谭月华(第四军医大学药理教研室,1西京医院临床药理室;2西北大学化学系,西安710032,中国)关键词心房;电刺激;甲基组胺;组胺拮抗剂;去甲肾上腺素;节后交感神... 展开更多
关键词 心房 电刺激 组胺 去甲肾上腺素 h3受体
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