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Influence of low dietary histamine on the seizure development of chemical kindling induced by pentylenetetrazol in rats

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Acta Pharmacologica Sinica 2005年第4期26卷 423-427页

作者： Eiko SAKURAI yoshinobu kiso Kazuhiko YANAI Department of Pharmacology Tohoku University School of Medicine Sendai 980-8575 Japan Department of Pharmacology School of Medicine Zhejiang University Hangzhou 310031 China Department of Pharmacologv School of Medicine Zhejiang University Hangzhou 310031 China Department of Pharmacology Tohoku University School of Medicine Sendai 980-8575 Japan

Aim:To determine the role of dietary low histamine on the seizure development ofpentylenetetrazol (PTZ)-induced kindling in ***:After 14 d of feedingon a low histamine diet (LH,containing 0.145 μmol/g of histamine),the rats werechemically kindled by repeated intraperitoneal injection of a subconvulsant doseof PTZ (35 mg/kg) once every 48 h,and seizure activity of kindling was recordedfor 30 *** in brain samples was analyzed using a high performanceliquid chromatography system with a fluorescence ***:The LH diet induced an increase in seizure response (seizure susceptibility) to thefirst trial of PTZ,and resulted in facilitation of subsequent PTZ kindling process(seizure development).The histamine levels in the cortex,hippocampus,andhypothalamus of LH-treated rats decreased significantly and these changes cor-related 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 contentin the cortex and hypothalamus in the LH-fed ***:These find-ings indicate that the histamine in daily food could influence the brain histaminer-gic function,and play an important role in regulating seizure susceptibility.

关键词： seizures pentylenetetrazol brain histamine diet

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Pharmacological effects of carcinine on histaminergic neurons in the brain

Pharmacological effects of carcinine on histaminergic neuron...

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首届长三角科技论坛——长三角生物医药发展论坛

作者： yoshinobu kiso Kazuhiko Yanai Suntory Co.Ltd Shimamoto-choOsaka 618-0012Japan Department of Pharmacology Tohoku University School of MedicineSendai 980-8575Japan

1 Carcinine(beta-alanyl histamine)is an imidazole *** present study was designedto characterize the pharmacological effects of carcinine on histaminergic activity in the brain andon certain neurobehavior.2 Carcinine was highly selective for the histamine 1-I3 receptor over H1 or H2 receptor [Ki (laM)= 0.2939 0.2188 vs. 3621.2 583.9 or 365.3 232.8 M, respectively].3 Carcinine, at a dose of 20 mg kg-slightly increased histidine decarboxylase (HDC) activity inthe cortex (from 0.186 0.069 pmol mg protein"l min1 to 0.227 0.009 pmol mg protein"1 rein’l).In addition, carcinine (10, 20 and 50 mg kg"1) significantly decreased histamine levels in micebrain.4 Like thioperamide, a histamine Ha receptor antagonist, carcinine (20, 50 gM) significantlyincreased 5-HT release from mice cortex slices, but had no apparent effect on dopamine release.5 Carcinine (20 mg kg1) significantly inhibited pentylenetetrazole- induced kindling. Thisinhibition was completedly reversed by (R)-methylhistamine, a representative Ha receptoragonist, and ot-fluromethylhistidine, a selective histidine decarboxylase inhibitor.6 The results of this study provide first and direct evidence that carcinine, as a novel histamineHa receptor antagonist, plays an important role in histaminergic neurons activation and might beuseful in the treatment of certain diseases, such as epilepsy.

关键词： histamine carcinine histamine H3 receptor locomotor activity seizure learning

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