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Hiroshima-shi, Japan

Ohtani M.,Osaka Dental University | Oka T.,Wakunaga Pharmaceutical Co. | Ohura K.,Osaka Dental University
General and Comparative Endocrinology | Year: 2013

Adenosine A1, A2A, A2B and A3 receptor mRNAs were found to be expressed in mouse pancreatic islets and Beta-TC6 cells but their physiological or pharmacological actions are not fully clarified. We showed that adenosine (100μM) augmented insulin secretion by islets in the presence of either normal (5.5mM) or a high concentration of glucose (20mM). The augmentation of insulin secretion in the presence of high glucose was blocked by an A2A antagonist, but not by A2B and A3 antagonists, while an A1 antagonist potentiated the adenosine effect. An adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) as well as A1, A2A and A3 receptor agonists also produced stimulation. On the other hand, an A3 agonist markedly reduced Beta-TC6 cell proliferation and the islet cell viability, while adenosine and NECA did not. The effect of A3 agonist was partially blocked by the A3 antagonist. In addition, treatment with the A3 agonist produced a small but significant extent of apoptosis in Beta-TC6 cells as judged by terminal transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. These results combined together suggested that like the A1 receptor, activation of A2A receptors by adenosine results in augmented insulin secretion, while the A3 receptor is involved in modulation of the survival of pancreatic β-cells. © 2013 Elsevier Inc.


Yano K.,Chiba University | Sekine S.,Chiba University | Nemoto K.,Chiba University | Fuwa T.,Wakunaga Pharmaceutical Co. | Horie T.,Chiba University
Biochemical Pharmacology | Year: 2010

Oxidative stress is known to be a common feature of cholestatic syndrome. Lipopolysaccharide (LPS) induces cholestasis, causing multidrug resistance-associated protein 2 (Mrp2) downregulation in two different ways: early retrieval from the canalicular membrane and the latter event of reduced mRNA expression. However, the triggering factor for LPS-induced cholestasis is not fully understood.In this study, we examined the effect of dimerumic acid (DMA), an antioxidant and traditional Chinese medicine, on endotoxin-induced Mrp2 downregulation in rat liver. At 3. h following LPS injection (4. mg/kg body weight), canalicular Mrp2 localization was disrupted without changing the expression of Mrp2 protein or the integrity of tight junctions in the liver. Pretreatment with DMA (12. mg/kg body weight) counteracted LPS-induced subcellular distribution, and decreased the bile flow rate and biliary glutathione (GSH) excretion. At 12. h following LPS injection, Mrp2 protein and mRNA expression were significantly decreased by 58% and 7%, respectively. In contrast, pretreatment with DMA did not have any effect on the decreased Mrp2 expression and biliary excretion of GSH induced by LPS exposure. Taken together, our data clearly indicate that LPS-induced short-term rapid retrieval of Mrp2 from the canalicular surface resulted from LPS-induced oxidative stress, while the long-term transcriptional regulation of Mrp2 expression did not depend on the intracellular redox status. © 2010 Elsevier Inc.


Iwata H.,Wakunaga Pharmaceutical Co. | Iwata H.,French National Institute for Agricultural Research | Gaston A.,French National Institute for Agricultural Research | Remay A.,French National Institute for Agricultural Research | And 8 more authors.
Plant Journal | Year: 2012

Flowering is a key event in plant life, and is finely tuned by environmental and endogenous signals to adapt to different environments. In horticulture, continuous flowering (CF) is a popular trait introduced in a wide range of cultivated varieties. It played an essential role in the tremendous success of modern roses and woodland strawberries in gardens. CF genotypes flower during all favourable seasons, whereas once-flowering (OF) genotypes only flower in spring. Here we show that in rose and strawberry continuous flowering is controlled by orthologous genes of the TERMINAL FLOWER 1 (TFL1) family. In rose, six independent pairs of CF/OF mutants differ in the presence of a retrotransposon in the second intron of the TFL1 homologue. Because of an insertion of the retrotransposon, transcription of the gene is blocked in CF roses and the absence of the floral repressor provokes continuous blooming. In OF-climbing mutants, the retrotransposon has recombined to give an allele bearing only the long terminal repeat element, thus restoring a functional allele. In OF roses, seasonal regulation of the TFL1 homologue may explain the seasonal flowering, with low expression in spring to allow the first bloom. In woodland strawberry, Fragaria vesca, a 2-bp deletion in the coding region of the TFL1 homologue introduces a frame shift and is responsible for CF behaviour. A diversity analysis has revealed that this deletion is always associated with the CF phenotype. Our results demonstrate a new role of TFL1 in perennial plants in maintaining vegetative growth and modifying flowering seasonality. © 2011 INRA. The Plant Journal © 2011 Blackwell Publishing Ltd.


Patent
Wakunaga Pharmaceutical Co. | Date: 2012-05-30

A method is provided for producing a sugar-coated preparation including a solid composition containing a pharmacologically active ingredient and a sugar coating layer. The method comprises a step of forming the sugar coating layer with a sugar coating composition containing one or more sugar-alcohols selected from the group consisting of mannitol and erythritol and a polyvinyl alcohol-based resin. The sugar-coated preparation includes a solid composition containing a pharmacologically active ingredient and a sugar coating layer, wherein the sugar coating layer is made of a sugar coating composition containing one or more sugar-alcohols selected from the group consisting of mannitol and erythritol and a polyvinyl alcohol-based resin.


Background: Garlic and its processed preparations contain numerous sulfur compounds that are difficult to analyze in a single run using HPLC. Objective: The aim of this study was to develop a rapid and convenient sulfur-specific HPLC method to analyze sulfur compounds in aged garlic extract (AGE). Methods: We modified a conventional postcolumn HPLC method by employing a hexaiodoplatinate reagent. Identification and structural analysis of sulfur compounds were conducted by LC-mass spectrometry (LC-MS) and nuclear magnetic resonance. The production mechanisms of cis-S-1-propenylcysteine (cis-S1PC) and S-allylmercaptocysteine (SAMC) were examined by model reactions. Results: Our method has the following advantages: Less interference from nonsulfur compounds, high sensitivity, good correlation coefficients (r > 0.98), and high resolution that can separate > 20 sulfur compounds, including several isomers, in garlic preparations in a single run. This method was adapted for LC-MS analysis. We identified cis-S1PC and γ-glutamyl- S-allyl-mercaptocysteine in AGE. The results of model reactions suggest that cis-S1PC is produced from trans-S1PC through an isomerization reaction and that SAMC is produced by a reaction involving S-allylcysteine/S1PC and diallyldisulfide during the aging period. Conclusion: We developed a rapid postcolumn HPLC method for both qualitative and quantitative analyses of sulfur compounds, and this method helped elucidate a potential mechanism of cis-S1PC and SAMC action in AGE. © 2016 American Society for Nutrition.

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