Pharmacology of GPR55 in Yeast and Identification of GSK494581A as a Mixed-Activity Glycine Transporter Subtype 1 Inhibitor and GPR55 Agonist
Andrew J. BrownDion A. DanielsMumta KassimSue BrownCarl HaslamVictoria R. TerrellJason BrownPaula L. NicholsPenny C. StatonAlan WiseSimon J. Dowell
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GPR55 is a G protein-coupled receptor activated by l-α-lysophosphatidylinositol and suggested to have roles in pain signaling, bone morphogenesis, and possibly in vascular endothelial cells. It has affinity for certain cannabinoids (molecules that interact with the cannabinoid CB1 and CB2 receptors), but investigation of its functional role in cell-based systems and in tissue has been limited by a lack of selective pharmacological tools. Here, we present our characterization of GPR55 in the yeast Saccharomyces cerevisiae and in human embryonic kidney (HEK293) cells. We describe GSK494581A (1-{2-fluoro-4-[1-(methyloxy)ethyl]phenyl}-4-{[4′-fluoro-4-(methylsulfonyl)-2-biphenylyl]carbonyl}piperazine), a selective small-molecule ligand of GPR55 identified through diversity screening. GSK494581A is one of a series of benzoylpiperazines originally identified and patented as inhibitors of the glycine transporter subtype 1 (GlyT1). The structure–activity relationship between GPR55 and GlyT1 is divergent across this series. The most GPR55-selective example is GSK575594A (3-fluoro-4-(4-{[4′-fluoro-4-(methylsulfonyl)-2-biphenylyl]carbonyl}-1-piperazinyl)aniline), which is approximately 60-fold selective for GPR55 (pEC50 = 6.8) over GlyT1 (pIC50 = 5.0). Several exemplars with activity at GPR55 and GlyT1 have been profiled at a broad range of other molecular targets and are inactive at cannabinoid receptors and all other targets tested. The benzoylpiperazine agonists activate human GPR55 but not rodent GPR55, suggesting that the relatively low level of sequence identity between these orthologs (75%) translates to important functional differences in the ligand-binding site.Keywords:
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Two kinds of miso, one with added precultured yeast and the other without, were compared with respect to the changes in the concentration of HEMF formed and the number of yeast cells in the process of aging. In miso without added yeast, the HEMF concentration increased with the increasing number of existing yeast cells. In miso without yeast aged for 21 days after the miso mash, 0.06 ppm HEMF was detected when the cell number was 2.2 × 103 cell/g. In yeast-added miso aged for 7 days after the miso mash, no HEMF was detected, although the number of yeast cells was 1.6 × 106 cell/g. In yeast-added miso aged for 14 days after the miso mash, HEMF was first detected. The pH levels of miso without yeast and with added yeast when HEMF was first detected were 5.59 and 5.57, respectively. It is suggested that the formation of HEMF in miso containing a high concentration of reducing sugar and salt was related to the growth of yeast and started when the pH level fell to less than 5.6.
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The article contains sections titled: 1. Introduction 2. The Yeast Cell 3. Food and Feed Yeast 3.1. Composition 3.2. Use of Yeast as a Major Protein Source 3.3. Production of Biomass 3.3.1. Baker's Yeast 3.3.2. Active Dry Yeast 3.3.3. Candida utilis (Torula) Yeast 3.3.4. Dairy Yeasts 3.3.5. Brewer's Yeast 3.3.6. Wine Yeasts 3.3.7. Distiller's Yeasts 4. Yeast-Derived Products 4.1. Flavor Products 4.2. Nutritional Yeast 4.3. Colorants Derived from Yeast 4.4. Yeast-Derived Enzymes 4.5. Pharmaceutical and Cosmetic Products
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Abstract In this investigation, the reactivation of the Mexican brewer's yeast dehydrated by spray drying as a way of generating cells with metabolic activity similar to the fresh yeast was studied. Fresh yeast, dehydrated-reactivated yeast, and unreactivated-dehydrated yeast were used. During the fermentation, fresh and dehydrated-reactivated yeast presented a greater growth rate than dehydrated yeast. Slow rehydration allowed an increase in alcohol production than that observed in a rapid rehydration. The sugars were metabolized faster by fresh than by dehydrated-reactivated, but this was faster than unreactivated-dehydrated yeast. The pH evolution did not show significant differences (α = 0.05) among yeasts. The reactivation was important for the yeast metabolic activity. Keywords: Brewery yeastFermentationMetabolic activitySpray drying ACKNOWLEDGEMENT The authors express acknowledge to the Mexican Consejo Nacional de Ciencia y Tecnología (CONACyT) by the financial support of this research.
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Yeast grown in synthetic medium produces in the medium a substance which inhibits yeast growth. Centrifugate from yeast growth medium taken during the exponential phase of growth increased indefinitely the lag phase of a newly seeded yeast. Added sugar and growth factors had no beneficial effect.
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We developed a yeast two-hybrid assay using a human-type estrogen receptor (hERα) to screen test chemicals reporting weak estrogenic activity at high concentrations. As a result of exposure to several test chemicals, viable yeast cells showed a decrease in number compared with a control. It was shown that this phenomenon was due to fungicidal effects of the test chemicals within the yeast cell or to inhibition of yeast cell proliferation. Therefore, in performing a yeast two-hybrid assay, it is necessary to monitor yeast cell proliferation by methods such as the measurement of the number of viable cells, and it is necessary to screen test chemicals within a concentration range where these chemicals show neither fungicidal effects towards the yeast cell nor inhibition of yeast cell proliferation.
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The amino acid glycine is an inhibitory neurotransmitter in the spinal cord, brain stem, and vertebrate retina. The effective synaptic concentrations of glycine are regulated by at least two transporters: glycine transporter 1 and glycine transporter 2. Here, we show retinal expression of glycine transporter 1 by in-situ hybridization and of glycine transporter 2 by reverse transcriptase-PCR and in-situ hybridization. In-situ hybridization signals were observed in the ganglionar and inner nuclear layer as well as in the outer nuclear layer of the frog and rat retinas. In addition, accumulation of 3H-glycine was observed in isolated photoreceptor cells. The expression of these transporters in nonglycinergic cells suggests that they may also modulate electrical signals.
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The special flavor of beer was mainly dependent on the used yeast species.The main factors inluencing yeast properties covered: yeast species,yeast inoculation quantity,use algebra of yeast,and fermentation technical conditions etc.The following yeast species was preferred for beer fermentation: yeast strain of low diacetyl yield and strong reductibility,and yeast of the second and the third generation had the strongest activity and reductibility.In practical production,lower inoculation temperature was adopted and adequate enhance of yeast inoculation quantity was recommended.Besides,strict technical operation was required.(Tran.by YUE Yang)
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