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OBJECTIVE: To investigate the effect of alahistidine on brain histamine content and seizure development. METHODS: The kindling seizure was induced by ip injection with subconvulsant dose of pentylenetetrazole every 48 h. Monoamines and their metabolites were measured using a HPLC system and fluorometric assay. RESULT: Chronic low histamine feeding markedly decreased histamine content in cortex and hypothalamus, and promoted seizure development induced by pentylenetetrazole. However, alahistidine feed reversed the decreased histamine content and slowed seizure development caused by low histamine feed. Both low histamine and alahistidine feed had no effect on norepinephrine, dopamine and its metabolites. CONCLUSION: Alahistidine may affect histaminergic system and seizure development.
Other papers by authors:AIM: To determine the role of dietary low histamine on the seizure development of pentylenetetrazol (PTZ)-induced kindling in rats. METHODS: After 14 d of feeding on a low histamine diet (LH, containing 0.145 mumol/g of histamine), the rats were chemically kindled by repeated intraperitoneal injection of a subconvulsant dose of PTZ (35 mg/kg) once every 48 h, and seizure activity of kindling was recorded for 30 min. Histamine in brain samples was analyzed using a high performance liquid chromatography system with a fluorescence spectrofluorometer. RESULTS: The LH diet induced an increase in seizure response (seizure susceptibility) to the first trial of PTZ, and resulted in facilitation of subsequent PTZ kindling process (seizure development). The histamine levels in the cortex, hippocampus, and hypothalamus of LH-treated rats decreased significantly and these changes correlated well with seizure behavior (r = 0.875, 0.651, and 0.796, respectively). In addition, chronic kindled seizures resulted in a significant increase of the histamine content in the cortex and hypothalamus in the LH-fed groups. CONCLUSION: These findings indicate that the histamine in daily food could influence the brain histaminergic function, and play an important role in regulating seizure susceptibility.
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China, 310058.
1. The present study examined the roles of hippocampal histaminergic system in the regulation of spatial memory deficit of rats induced by scopolamine infusion into bilateral dorsal hippocampus (DH) or ventral hippocampus (VH) using radial-arm maze task. 2. Both bilateral dorsal and ventral hippocampal injections of scopolamine impaired spatial memory in retrieval memory process. Dorsal hippocampal injection of histamine and intraperitoneal injection of histidine markedly improved working memory and reference memory deficits induced by scopolamine administered in the DH. Histamine H(1) antagonist pyrilamine abolished the ameliorative effect of histidine on working memory deficits, while both pyrilamine and H(2) antagonist cimetidine abolished the effect of histidine on reference memory. Local injection of histamine in the VH and systemic injection of histidine markedly improved working memory deficits induced by scopolamine administered in the VH, but did not improve the insulted reference memory deficits. Both ventral hippocampal administration of pyrilamine and cimetidine reversed the effect of histidine. 3. The results indicate that histamine exerts different functions in cholinergic related memory in the DH and VH. Histamine in the DH ameliorates spatial working memory deficits by acting on H(1) receptors and reference memory deficits through H(1 )and H(2) receptors. Histamine in the VH ameliorates working memory deficits via both H(1) and H(2) receptors.
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China. chenzhong@zju.edu.cn.
Aim: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. Methods: An 8-arm radial maze (4 arms baited) was used to assess spatial memory. Results: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 mug/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 mug/site, ih) and the H2 antagonist cimetidine (2.5 mug/site, ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. Conclusion: The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.
Department of Pharmacology, Zhejiang University, Hangzhou 310031, China.
AIM: To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. METHODS: Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and gamma-amino-butyric acid levels were measured by high performance liquid chromatography (HPLC). RESULTS: Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no ameliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures. CONCLUSION: Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.
Hongmei Dai,
Hirotomo Okuda,
Kentaro Iwabuchi,
Eiko Sakurai,
Zhong Chen,
Motohisa Kato,
Kazuie Iinuma,
Kazuhiko Yanai
Department of Pharmacology, Tohoku University School of Medicine, Sendai 980-8575, Japan.
Repeated administration of methamphetamine (METH) causes reverse tolerance or behavioral sensitization in mice. However, the effects of social isolation stress on the METH-caused reverse tolerance have not been studied until now. The aim of this study was to investigate the effects of social isolation stress on METH-caused reverse tolerance by examining the prepulse inhibition of startle response (PPI). PPI was tested in socially isolated and grouped mice after repeated METH injections. Locomotor activity and PPI were also examined just after a four-week isolation rearing period as a control experiment. After completing behavioral experiments, the mice were sacrificed, and the contents of monoamines, including histamine in the brain, were measured. Social isolation stress significantly lowered the locomotion and disrupted PPI. Repeated injections of METH enhanced the effects of social isolation on PPI. The content of dopamine and histamine significantly increased in the cortex, and the turnover rate of dopamine decreased significantly. These findings demonstrate that social isolation stress significantly enhances METH-induced behavioral sensitization and that the altered histaminergic neuron system might play an important role in METH-induced behavioral sensitization in addition to dopaminergic and serotoninergic neurotransmission. Our data suggest that social isolation is involved in the development of METH-induced psychosis, schizophrenia, and other related psychiatric disorders.
Zhong Chen,
Eiko Sakurai,
Weiwei Hu,
Chunlei Jin,
Yoshinobu Kiso,
Motohisa Kato,
Takehiko Watanabe,
Erqing Wei,
Kazuhiko Yanai
Department of Pharmacology, Tohoku University School of Medicine, Sendai 980-8575, Japan. chenzhong@zju.edu.cn
1 Carcinine (beta-alanyl histamine) is an imidazole dipeptide. The present study was designed to characterize the pharmacological effects of carcinine on histaminergic activity in the brain and on certain neurobehavior. 2 Carcinine was highly selective for the histamine H3 receptor over H1 or H2 receptor (Ki (microM)=0.2939+/-0.2188 vs 3621.2+/-583.9 or 365.3+/-232.8 microM, respectively). 3 Carcinine at a dose of 20 mg kg(-1) slightly increased histidine decarboxylase (HDC) activity in the cortex (from 0.186+/-0.069 to 0.227+/-0.009 pmol mg protein(-1) min(-1)). In addition, carcinine (10, 20, and 50 mg kg(-1)) significantly decreased histamine levels in mice brain. 4 Like thioperamide, a histamine H3 receptor antagonist, carcinine (20, 50 microM) significantly increased 5-HT release from mice cortex slices, but had no apparent effect on dopamine release. 5 Carcinine (20 mg kg(-1)) significantly inhibited pentylenetetrazole-induced kindling. This inhibition was completely reversed by (R)-alpha-methylhistamine, a representative H3 receptor agonist, and alpha-fluromethylhistidine, a selective HDC inhibitor. 6 Carcinine (20 mg kg(-1)) ameliorated the learning deficit induced by scopolamine. This amelioration was reversed by (R)-alpha-methylhistamine as evaluated by the passive avoidance test in mice. 7 Like thioperamide, carcinine dose-dependently increased mice locomotor activity in the open-field test. 8 The results of this study provide first and direct evidence that carcinine, as a novel histamine H3 receptor antagonist, plays an important role in histaminergic neurons activation and might be useful in the treatment of certain diseases, such as epilepsy, and locomotor or cognitive deficit.
OBJECTIVE: To investigate the effects and the mechanisms of the first-generation histamine H(1)-antagonist diphenhydramine and the second-generation histamine H(1)- antagonist fexofenadine on seizure development of pentylenetetrazole (PTZ)-induced kindling in rats. METHODS: The first-or second-generation histamine H(1)-antagonists and/or histidine were ip injected in rats every 48 h, followed by a subconvulsive dose of PTZ (35 mg/kg). Then the behavioral changes were observed for 30 min after every injection of PTZ. The histamine content of brain was measured spectrofluorometrically. RESULT: Compared with the control group, diphenhydramine (5 mg/kg) significantly augmented the severity of seizure development of PTZ-induced kindling, whereas fexofenadine (5 mg/kg) had no marked influence. The effects of diphenhydramine were antagonized by histidine, the precursor of histamine. CONCLUSION: Seizure development of PTZ-induced kindling is promoted by the first-but not the second generation histamine H(1)-antagonists via the blockade of brain histamine H(1)-receptor.
OBJECTIVE: To investigate the mechanisms of histamine on chronic epilepsy induced by pentylenetetrazole (PTZ). METHODS: To induce chemical kindling, a subconvulsive dose (35mg/kg) of PTZ was ip injected every 48 h in rats. Behavior changes were observed for 30 min after every injection of PTZ. RESULT: Ip injection of histidine or icv injection of clobenpropit inhibited the development of kindling induced by PTZ, presenting prolonged latency for myoclonic jerks and clonic generalized seizures and depressed seizure stages in a dose-dependent manner. H(3)receptor agonist, immepip, and histidine decarboxylase, alpha-fluoromethylhistidine reversed the ameliorating effect of clobenpropit on seizure development in a dose-dependent manner. CONCLUSION: Brain histamine plays an important role in protection against myoclonic jerks and clonic generalized clonic seizures and its action may be via H(3)receptor.
OBJECTIVE: To investigate changes of brain mast cells after transient global ischemia in rats. METHODS: Transient global ischemia damage was induced by four-vessel occlusion. After 1 h to 14 days of ischemia, rats were perfused intracardially by 4% paraformaldehyde. The brains were dissected to serial sections using freeze microtome, and then stained with toluidine blue. Brain mast cell was observed under microscope. RESULT: Most brain mast cells were located in thalamus. The number of mast cells in thalamus markedly decreased during reperfusion after transient global ischemia. However, the degranulation rate of thalamus mast cells showed reverse change after ischemia. CONCLUSION: Brain mast cells markedly degranulate after transient global ischemia, which may be involved in the pathological process after ischemia.
Yu-Wen Huang,
Wei-Wei Hu,
Zhong Chen,
Li-San Zhang,
Hai-Qing Shen,
Henk Timmerman,
Rob Leurs,
Kazuhiko Yanai
Department of Pharmacology and Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
This study was performed to investigate whether or not the histamine H(3)-antagonist clobenpropit can ameliorate spatial memory deficits induced by MK-801 (0.3microg per site) as evaluated by an eight-arm radial maze task of rats. A bilateral intrahippocampal (i.h.) injection of clobenpropit (5, 10microg per site, dose-dependent) markedly improved the working and reference memory deficits induced by MK-801. Its ameliorating effect was potentiated by histidine, but completely antagonized by immepip (2.5microg per site), a selective H(3)-agonist. alpha-Fluoromethylhistidine (FMH, 25microg per site), a selective histidine decarboxylase inhibitor prevented the ameliorating effect of clobenpropit on the working memory deficits induced by MK-801. In addition, the H(1)-antagonist pyrilamine, but not the H(2)-antagonist cimetidine, also inhibited the procognitive effects of clobenpropit. Both FMH and pyrilamine did not significantly modulate the effect of clobenpropit on reference memory. Therefore, the results of this study suggest that the procognitive effects of clobenpropit in MK-801-induced working memory deficits is mediated by increasing endogenous histamine release. In addition, the ameliorating effect of clobenpropit on reference memory might be due to the increased release of neurotransmitters other than histamine.
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Sichuan Academy of Traditional Chinese Medicine Sciences, Chengdu 610041, China.
OBJECTIVE: To study the effect of different seminal rhizomes on the growth, quality and quantity of Curcuma longa root. METHOD: Single factor randomized block design was applied, plant samples were collected and investigated periodically, and dry weight, production and the main active ingredient content were measured. RESULT: The difference seminal rhizomes affected the growth, quality and quantity of C. longa root. CONCLUSION: The bigger and stronger rhizomes should be chosen as seeds.
OBJECTIVE: To investigate the anti-aging effect of aqueous extract of Hedysarum austrosibiricum cultivated in Xin-jiang. METHOD: Subacute aging model in mice was established by D-galactose (D-gal) and activities of SOD and GSH-PX, contents of MDA in brain and liver tissues, activities of MAO in brain tissue and immune indexes were determined. RESULT: Aqueous extract of H. austrosibiricum Xinjiang markedly increased the activities of SOD and GSH-PX, significantly decreased contents of MDA in brain and liver tissues. MAO activities in brain tissue were also decreased. It also elevated the spleen and thymus indexes. CONCLUSION: Aqueous extract of H. austrosibiricum might have anti-aging effect, which is implemented by eliminating oxyen free radicals, rising activities
OBJECTIVE: To investigate the mechanism of the apoptosis-inducing effects of dopamine on K562 leukemia cells. METHODS: K562 cells were treated with DP2785, the dopamine receptors were detected with fluorescence spectrophotometer, UV spectrophotometer and fluorescence microscope; the contents of cAMP in K562 cells were measured; and the subtypes of dopamine receptor on K562 cells were analyzed by receptor blocking. RESULT: The existence of dopamine receptors in K562 cells was demonstrated by fluorescence microscopy, UV spectrophotometer and fluorescence spectrophotometer. Dopamine enhanced the contents of cAMP in K562 cells. Dopamine receptors were blocked by both D1 and D2 antagonists. CONCLUSION: D1 and D2 dopamine receptors may be involved in dopamine-induced apoptosis of K562 cells, and dopamine can also increase the contents of cAMP in K562 cells.
Key Laboratory for Biomechanics and Tissue Engineering under the State Ministry of Education, College of Bioengineering, Chongqing University, China.
OBJECTIVE: To detect the polysaccharides content of tissue culturing seedlings on Dendrobium candidium under special sound wave stimulation. METHODS: The content of polysaccharides was detected by phenol-vitriol colorimetry method. RESULTS: The polysaccharides content of the groups stimulated continuously for 24d was higher obviously than the content of the control groups. CONCLUSION: The stimulation of the special sound wave promoted markedly the synthesis of polysaccharides in D. candidium. It may affect obviously the metabolic pathway of polysaccharides in D. candidium.
Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
OBJECTIVE: To investigate the effect of andrographolide on virulence factors production in Pseudomonas aeruginosa. METHOD: Growth rate, pyocyanin, proteolytic activity and elastase activity were measured with or without the presence of andrographolide. The effect of andrographolide on pyocyanin production, proteolytic activity and elastase activity in PAO-JP2 was investigated simultaneously. RESULT: The andrographolide did not affect the growth of PAO1 in planktonic culture. The production of pyocyanin, proteolytic activity and elastase activity were significanthy suppressed in P. aeruginosa cultures grown in the presence of andrographolide. However, these effects were not observed in PAO-JP2. CONCLUSION: The inhibiting effect of andrographolide on virulence factors production in P. aeruginosa may play a role in its anti-infection activity.
Takae Ebihara,
Satoru Ebihara,
Aya Watando,
Tatsuma Okazaki,
Masanori Asada,
Takashi Ohrui,
Mutsuo Yamaya,
Hiroyuki Arai
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
Aims: To investigate the effect of menthol on swallowing reflex sensitivity in elderly patients with dysphagia. Methods and results: The swallowing reflex sensitivity of institutionalized elderly patients was evaluated as a latent time of swallowing reflex (LTSR), induced by the injection of 1 ml solution into the pharynx. LTSR was significantly shortened in a concentration-dependent manner, from 13.8 s [95% confidence interval (CI) 11.1, 16.5] by distilled water to 9.4 s (95% CI 7.1. 11.8) by 10(-2)m menthol. Conclusion: Using menthol with elderly patients with dysphagia may improve the sensitivity of their swallowing reflex, resulting in prevention of aspiration pneumonia.
Guangzhou University of Traditional Chinese Medicine, Guangzhou.
OBJECTIVE:(1) To study the effect of concentration and flow rate on relative recovery (RR);(2) To study the difference Of relative recovery between probes;(3) To study the relationship between relative recovery and relative loss (RL). METHODS: HPLC. RESULTS:(1) The sinomenine concentration has no obvious effect on RR in the same flow rate.(2) RR is reduced by exponent law as the flow rate increases.(3) There is significent difference between probes. CONCLUSION: The RR isn't affected by sinomenine concentration as the flow rate is same. The flow rate has notable effect on RR as the sinomenine concentration is same. The RR of every probe should be assayed. We can take RL as RR to do in-vivo study.
Pharmacy School, Shanghai Jiao Tong University, Shanghai.
OBJECTIVE: To investigate the possible effect of antidepressant effect of total triterpentes of Centella asiatica. METHODS: The corticosterone levels in serum were measured by fluorescence spectroscopy. The contents of monoamine neurotransmitters and their metabolites in rats cortex, hippocamopus and thalamus were evaluated by using HPLC with electrochemical detector. RESULTS: Significant reduction of the corticosterone level in serum and increase of the contents of 5-HT, NE, DA and their metabolites 5-HIAA, MHPG in rat brain were observed. CONCLUSION: The antidepressant effect of total triterpenes of Centella asiatica may be involved in ameliorating the function of HPA axis and increasing the contents of monoamine neurotransmitters.
OBJECTIVE: To explore the effect of extract from Chinese chive seed in warming kidney and enhancing yang. METHOD: The influence of extract from Chinese chive seed on the erection of penis of was investigated in adult male rats with experimental insufficiency of the kidney-yang produced by both removal of double spermaries and high dose of hydrocortisone. RESULT: The extract of Chinese chive seed enhanced the responsiveness of the penis of emasculate rats to outside stimulus, promoted the resistance of the emasculated rats to cold and tiredness and increased autonomous activity. CONCLUSION: The extract of Chinese chive seed has the effect of warming kidney and enhancing yang.
Bozena Witek,
Ewa Ochwanowska,
Jan Rafay,
Adam Kolataj,
Peter Chrenek,
Karin Suvegova,
Rastislav Jurcik,
Alexander Sirotkin,
Krzysztof Darlak
Department of Genetics, Institute of Biology, Swietokrzyska Academy, Kielce, Poland. b.witek@pu.kielce.pl
OBJECTIVES: Observing the changes of activity of some lysosomal enzymes in blood serum of female rabbits subjected to injection of 10 microg of ghrelin/kg of body weight. METHODS: In the blood serum the activity of cathepsins D and L, alanine aminopeptidase, acid phosphatase, lysosomal lipase and lysosomal esterase was determined. RESULTS: As a result of ghrelin injection the activity of all the enzymes examined in blood serum increased markedly. CONCLUSION: Changes of lysosomal enzymes activities in the blood serum caused by the effects of ghrelin should be regarded as the response of the lysosomal system.
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