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71.
Ge H Weiszmann J Reagan JD Gupte J Baribault H Gyuris T Chen JL Tian H Li Y 《Journal of lipid research》2008,49(4):797-803
GPR81 is an orphan G protein-coupled receptor (GPCR) that has a high degree of homology to the nicotinic acid receptor GPR109A. GPR81 expression is highly enriched and specific in adipocytes. However, the function and signaling properties of GPR81 are unknown because of the lack of natural or synthetic ligands. Using chimeric G proteins that convert Gi-coupled receptors to Gq-mediated inositol phosphate (IP) accumulation, we show that GPR81 can constitutively increase IP accumulation in HEK293 cells and suggest that GPR81 couples to the Gi signaling pathway. We also constructed a chimeric receptor that expresses the extracellular domains of cysteinyl leukotriene 2 receptor (CysLT2R) and the intracellular domains of GPR81. We show that the CysLT2R ligand, leukotriene D(4) (LTD4), is able to activate this chimeric receptor through activation of the Gi pathway. In addition, LTD4 is able to inhibit lipolysis in adipocytes expressing this chimeric receptor. These results suggest that GPR81 couples to the Gi signaling pathway and that activation of the receptor may regulate adipocyte function and metabolism. Hence, targeting GPR81 may lead to the development of a novel and effective therapy for dyslipidemia and a better side effect profile than nicotinic acid. 相似文献
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73.
Zarnowski R Jaromin A Certik M Czabany T Fontaine J Jakubik T Iqbal MC Grandmougin-Ferjani A Kozubek A Pietr SJ 《Zeitschrift für Naturforschung. C, Journal of biosciences》2004,59(5-6):321-326
The oil of Adenanthera pavonina L. seeds was analysed by chromatographic and instrumental means. The oil was found to be rich in neutral lipids (86.2%), and low in polar lipids (13.8%). The neutral lipids consisted mainly of triacylglycerols (64.2%). Unsaturated fatty acids were found as high as 71%, while the percentage of saturated fatty acids was only 29%. GC and GC/MS analyses revealed linoleic, oleic and lignocerotic acid to be predominant among all fatty acids in the A. pavonina oil, whereas stigmasterol was the major steroid identified within this study. Subsequently, the oil was used for preparation of submicron oil-in-water (o/w) lipid emulsions. Lipid emulsions were formulated by using soybean lecithin (SL) to investigate their particle size, Zeta potential and stability at the different oil and SL ratios. The results obtained indicate possible applications of the tested oil in pharmaceutical and medical fields as drug and cosmetic active ingredient carriers. 相似文献
74.
Djinović V Momcilović M Grgurić-Sipka S Trajković V Mostarica Stojković M Miljković D Sabo T 《Journal of inorganic biochemistry》2004,98(12):2168-2173
A novel class of ruthenium (III) complexes of formulas K[Ru(sar)2Cl2].12H2O and K2[Ru(dmgly)Cl4].2H2O, containing bidentate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dmgly) and additional chloro ligands were synthesized. The complexes have been obtained by direct reaction of ruthenium(III) chloride with corresponding bidentate ligand followed by addition of base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. As astrocytomas, the most common of all brain tumors, are still very difficult to treat, we examined the influence of newly synthesized ruthenium-based complexes, as well as the earlier synthesized analogue platinum(IV) complexes [Pt(dmgly)2Cl2], [Pt(sar)2Br2] and [Pt(dmgly)2Br2], on rat astrocytoma C6 cells in vitro. Among these complexes only K2[Ru(dmgly)Cl4].2H2O and [Pt(dmgly)2Br2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K2[Ru(dmgly)Cl4].2H2O was able to reduce viability in confluent C6 cultures. Importantly, this complex was not toxic to primary rat astrocytes or macrophages. Having in mind that appropriate chemotherapy should be effective against tumor cells without harming normal tissues, complex K2[Ru(dmgly)Cl4].2H2O could be a promising agent for developing therapeutics against astrocytomas. 相似文献
75.
The mechanisms involved in the mediation of the inhibitory effects of ethanol on gastric emptying were studied in adult male rats. The gastric emptying was determined by measuring the amount of phenol red recovered from the stomach after intragastric administration. Intragastric administration of a 2.5 g kg(-1) body weight dose of ethanol resulted in inhibition of the gastric emptying. Prior intraperitoneal treatment with lorglumide (CR-1409), a selective CCK-A receptor antagonist, abolished the inhibitory effect of ethanol on the gastric emptying. This observation furnishes evidence indicative of the involvement of type A CCK receptors in the mediation of the inhibitory effect of large doses of ethanol on the gastric emptying. 相似文献
76.
Forgács E Cserháti T Miksik I Echardt A Deyl Z 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,800(1-2):259-262
The retention time of 22 barbituric acid derivatives was measured on a narrow-bore porous graphitized carbon (PGC) column using water-dioxane mixtures as mobile phases. The capacity factor (k), theoretical plate number (N), and asymmetry factor (AF) were calculated for each solute in each mobile phase. The relationships between chromatographic characteristics and physicochemical parameters of solutes were elucidated by stepwise regression analysis (SRA). SRA indicated that the binding of barbiturates to the PGC surface is of mixed character electrostatic and apolar interactive forces are equally involved. Sterical correspondence between the surface of the stationary phase and the solutes also exert a significant influence on the retention behavior. 相似文献
77.
Mikó T Ligneau X Pertz HH Arrang JM Ganellin CR Schwartz JC Schunack W Stark H 《Bioorganic & medicinal chemistry》2004,12(10):2727-2736
Recent bioisoteric replacements in histamine H3 receptor ligands with an exchange of the imidazole moiety by a piperidino group as well as of the trimethylene chain in 4-((3-phenoxy)propyl)-lH-imidazole derivatives (proxifan class) by an alpha,alpha'-xylendiyl linker represents the starting point in the development of 1-(4-(phenoxymethyl)benzyl)piperidines as a new class of nonimidazole histamine H3 receptor antagonists. According to different strategies in optimization of imidazole-containing antagonists the central benzyl phenyl ether moiety was replaced by numerous other polar functionalities. Additionally, the ortho- and meta-analogues of the lead were synthesized to determine the influence of the position of the piperidinomethyl substituent. The new compounds were tested in an in vitro binding assay for their affinities for cloned human H3 receptors stably expressed in CHO-K1 cells and for their oral in vivo potencies brain in a functional screening assay in the brain of mice. Additionally, activities of selected compounds were determined in the guinea-pig ileum functional test model. In contrast to the analogues ortho-substituted compounds all other compounds maintained respectable affinities for the human H3 receptor (-log Ki values 6.3-7.5). Despite the results from other classes of compounds the 4-methyl substituted derivatives generally displayed higher affinities than the corresponding 4-chloro substituted compounds. In vivo only the inverse phenyl benzyl ether (3) showed worthwhile antagonist potencies. 相似文献
78.
79.
Genetic rescue of chondrodysplasia and the perinatal lethal effect of cartilage link protein deficiency 总被引:1,自引:0,他引:1
Czipri M Otto JM Cs-Szabó G Kamath RV Vermes C Firneisz G Kolman KJ Watanabe H Li Y Roughley PJ Yamada Y Olsen BR Glant TT 《The Journal of biological chemistry》2003,278(40):39214-39223
80.