著者

丹羽 俊朗 柳井 檀 杉本 静也 雫 真里菜

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学会年会要旨集 第92回日本薬理学会年会 (ISSN:24354953)

巻号頁・発行日

pp.3-P-128, 2019 (Released:2020-03-20)

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[Purpose] CYP2D catalyze dopamine formation from p- and m-tyramine in the brain, and human CYP2D6 is polymorphic Imipramine, a tricyclic antidepressant, and fluvoxamine, an SSRI, are CYP2D6 inhibitors. Dopamine formation from p-tyramine mediated by CYP2D6 variants, CYP2D6.2 and CYP2D6.10 was compared, and the effect of genetic polymorphism on the inhibitory effects of antidepressants was investigated.[Methods] CYP2D6.1, CYP2D6.2, and CYP2D6.10 expressed in recombinant Escherichia coli were used. Dopamine formation from p-tyramine in the presence of antidepressants such as imipramine, desipramine, fluvoxamine, fluoxetine, and paroxetine was determined by HPLC.[Results] CYP2D6.10 had higher Michaelis constants of dopamine formation than CYP2D6.1 and CYP2D6.2. Inhibition constant of imipramine and desipramine against CYP2D6.10 were higher than that against CYP2D6.1. Fluoxetine and paroxetine inhibited CYP2D6.1-mediated dopamine formation. The maximal velocity for all CYP2D6 variants gradually increased with increasing fluvoxamine concentrations. [Conclusions] CYP2D6 polymorphism might affect the inhibitory effect of antidepressants on dopamine formation in the brain.

著者

井上 里加子 小川 亜紀 吉村 征浩 入江 康至

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学会年会要旨集 第92回日本薬理学会年会 (ISSN:24354953)

巻号頁・発行日

pp.2-P-134, 2019 (Released:2020-03-20)

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There are two types of amazake: malted-rice amazake and Sake lees amazake. It has been reported that Sake lees amazake improves human intestinal flora and relieves constipation. But there is no report on malted-rice amazake for improving constipation. The purpose of this study is to conduct a long-term ingestion test on humans and consider whether intake of malted-rice amazake will improve constipation. The subject is adult females with periodic menstrual cycles. Feces were collected in the follicular phase to minimize the influence of premenstrual syndrome. The DNA extracts from feces were analyzed using quantitative PCR using specific primers. The defecation status was investigated by self-report questionnaire.In the defecation state, soft stool of the stool was found significantly by intake of malted-rice amazake in hard stool group. Symptoms of constipation improved in 83% of constipation group. Analysis of intestinal bacterial flora showed a significant decrease the ratio of Firmiscutes / Bacteroidetes in constipation group due to intake of malted-rice amazake. It was suggested that intake of malted-rice amazake changed the construction of gut microbiota as well as the intestinal environment, resulting in improvement in constipation.

著者

宮崎 育子 磯岡 奈未 和田 晃一 菊岡 亮 北村 佳久 浅沼 幹人

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学会年会要旨集 第92回日本薬理学会年会 (ISSN:24354953)

巻号頁・発行日

pp.2-P-050, 2019 (Released:2020-03-20)

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Epidemiological studies showed that daily drinking coffee or teas decreases the risk of Parkinson's disease (PD) to 40-50%. Caffeic acid (CA) and chlorogenic acid (CGA) are coffee ingredients and exert antioxidative properties. Exposure to pesticides, such as rotenone, is an environmental factor that plays an important role in the pathogenesis of PD. In this study, we examined neuroprotective effects of CA and CGA against rotenone-induced neurodegeneration. Chronic subcutaneous injection of rotenone into C57BL/6J mice exhibited reduction of dopaminergic neurons in the substantia nigra and beta-tubulin III-positive neurons in the intestinal myenteric plexus. Daily oral administrations of CA or CGA inhibited rotenone-induced cell death of not only nigral dopaminergic neurons but also myenteric plexus. In addition, CA or CGA significantly increased expression of antioxidative molecule metallothionein in the striatal astrocytes. In coculture of neurons and astrocytes from the mesencephalon or intestine, CA and CGA inhibited rotenone-induced neuronal loss of mesencephalic dopaminergic and enteric neurons, respectively. These results suggest that daily intake of coffee ingredients prevents or delays the onset of PD.

著者

金子 周司 長島 卓也

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学会年会要旨集 第92回日本薬理学会年会 (ISSN:24354953)

巻号頁・発行日

pp.2-AS1-2, 2019 (Released:2020-03-20)

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FAERS is a public database that accumulates more than 9 million self-reports of adverse events. In nearly half of the cases, multiple drugs are prescribed, so that potential drug-drug interactions are to be analyzed. Focusing on adverse reactions relating to diabetes mellitus (DM) caused by an anti-schizophrenic quetiapine, we found that concomitant use of vitamin D analogs significantly suppresses the occurrence of quetiapine-induced DM in FAERS. Experimental validation revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. In an expression database, several genes downstream of insulin receptor were downregulated by quetiapine. Further experiments clarified that a PI3K regulatory protein gene, pik3r1, was downregulated by quetiapine, which was reversed by cholecalciferol in mouse skeletal muscle. In addition, insulin-stimulated glucose uptake into cultured myotubes was inhibited by quetiapine, which was reversed by pretreatment with calcitriol. These results suggest that vitamin D prevents the atypical antipsychotic-induced hyperglycemia and insulin resistance by upregulation of PI3KR1. Until now, we have obtained several combinations of concomitant medications to reduce specific adverse events by FAERS analysis. This new strategy will pave the way for drug repositioning and clarifying unknown disease mechanisms.

著者

中尾 駿介 中道 範隆 増尾 友佑 竹田 有花 松本 聡 鈴木 真 加藤 将夫

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学会年会要旨集 第92回日本薬理学会年会 (ISSN:24354953)

巻号頁・発行日

pp.2-YIA-03, 2019 (Released:2020-03-20)

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The aim of the present study was to examine enhancement of learning and memory by oral administration of ergothioneine (ERGO), which is a hydrophilic antioxidant highly contained in golden oyster mushrooms and other foods, and systemically absorbed by its specific transporter OCTN1/SLC22A4 in daily life, with an aim to clarify its possible role as a neurotropic compound. After oral administration of ERGO in normal mice, the novel object test revealed a longer exploration time for the novel object than for the familiar object. Similar result was also confirmed in mice ingested with ERGO-free diet. Dietary-derived ERGO is present in the body without the administration, but the ERGO administration led to modest (3~4 times) increase in its concentration in plasma and hippocampus. Exposure of cultured hippocampal neurons to ERGO elevated the expression of the synapse formation marker, synapsin I, and neurotrophin-3 and -5. The elevation of synapsin I was inhibited by tropomyosin receptor kinase inhibitor K252a. Thus, oral intake of ERGO may enhance object recognition memory, and this could occur at least partially through promotion of neuronal maturation in the hippocampus.