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• W2589520828 endingPage "118" @default.
• W2589520828 startingPage "63" @default.
• W2589520828 abstract "A large problem of histamine receptor research is data heterogeneity. Various experimental approaches, the complex signaling pathways of mammalian cells, and the use of different species orthologues render it difficult to compare and interpret the published results. Thus, the four human histamine receptor subtypes were analyzed side-by-side in the Sf9 insect cell expression system, using radioligand binding assays as well as functional readouts proximal to the receptor activation event (steady-state GTPase assays and [35S]GTPγS assays). The human H1R was co-expressed with the regulators of G protein signaling RGS4 or GAIP, which unmasked a productive interaction between hH1R and insect cell Gαq. By contrast, functional expression of the hH2R required the generation of an hH2R-Gsα fusion protein to ensure close proximity of G protein and receptor. Fusion of hH2R to the long (GsαL) or short (GsαS) splice variant of Gαs resulted in comparable constitutive hH2R activity, although both G protein variants show different GDP affinities. Medicinal chemistry studies revealed profound species differences between hH1R/hH2R and their guinea pig orthologues gpH1R/gpH2R. The causes for these differences were analyzed by molecular modeling in combination with mutational studies. Co-expression of the hH3R with Gαi1, Gαi2, Gαi3, and Gαi/o in Sf9 cells revealed high constitutive activity and comparable interaction efficiency with all G protein isoforms. A comparison of various cations (Li+, Na+, K+) and anions (Cl-, Br-, I-) revealed that anions with large radii most efficiently stabilize the inactive hH3R state. Potential sodium binding sites in the hH3R protein were analyzed by expressing specific hH3R mutants in Sf9 cells. In contrast to the hH3R, the hH4R preferentially couples to co-expressed Gαi2 in Sf9 cells. Its high constitutive activity is resistant to NaCl or GTPγS. The hH4R shows structural instability and adopts a G protein-independent high-affinity state. A detailed characterization of affinity and activity of a series of hH4R antagonists/inverse agonists allowed first conclusions about structure/activity relationships for inverse agonists at hH4R. In summary, the Sf9 cell system permitted a successful side-by-side comparison of all four human histamine receptor subtypes. This chapter summarizes the results of pharmacological as well as medicinal chemistry/molecular modeling approaches and demonstrates that these data are not only important for a deeper understanding of HxR pharmacology, but also have significant implications for the molecular pharmacology of GPCRs in general." @default.
• W2589520828 created "2017-03-03" @default.
• W2589520828 creator A5040439170 @default.
• W2589520828 creator A5082356190 @default.
• W2589520828 date "2017-01-01" @default.
• W2589520828 modified "2023-09-26" @default.
• W2589520828 title "Pharmacological Characterization of Human Histamine Receptors and Histamine Receptor Mutants in the Sf9 Cell Expression System" @default.
• W2589520828 cites W1481471030 @default.
• W2589520828 cites W1492420937 @default.
• W2589520828 cites W1506519811 @default.
• W2589520828 cites W1511344849 @default.
• W2589520828 cites W1539774089 @default.
• W2589520828 cites W1572956640 @default.
• W2589520828 cites W1579793052 @default.
• W2589520828 cites W1608128587 @default.
• W2589520828 cites W1715602013 @default.
• W2589520828 cites W1805958564 @default.
• W2589520828 cites W1825353903 @default.
• W2589520828 cites W1873461223 @default.
• W2589520828 cites W1908561802 @default.
• W2589520828 cites W1933763619 @default.
• W2589520828 cites W1943636078 @default.
• W2589520828 cites W1956325971 @default.
• W2589520828 cites W1957990440 @default.
• W2589520828 cites W1960199343 @default.
• W2589520828 cites W1964677809 @default.
• W2589520828 cites W1965835906 @default.
• W2589520828 cites W1967584261 @default.
• W2589520828 cites W1968399191 @default.
• W2589520828 cites W1970332556 @default.
• W2589520828 cites W1970729674 @default.
• W2589520828 cites W1970741422 @default.
• W2589520828 cites W1971176660 @default.
• W2589520828 cites W1971657990 @default.
• W2589520828 cites W1975740938 @default.
• W2589520828 cites W1976447614 @default.
• W2589520828 cites W1977986244 @default.
• W2589520828 cites W1978283736 @default.
• W2589520828 cites W1978404758 @default.
• W2589520828 cites W1980629470 @default.
• W2589520828 cites W1983208716 @default.
• W2589520828 cites W1985972401 @default.
• W2589520828 cites W1989452809 @default.
• W2589520828 cites W1989578166 @default.
• W2589520828 cites W1990502478 @default.
• W2589520828 cites W1991163722 @default.
• W2589520828 cites W1996480595 @default.
• W2589520828 cites W1999076037 @default.
• W2589520828 cites W1999279782 @default.
• W2589520828 cites W1999355237 @default.
• W2589520828 cites W2001079294 @default.
• W2589520828 cites W2001908693 @default.
• W2589520828 cites W2002476870 @default.
• W2589520828 cites W2009120970 @default.
• W2589520828 cites W2010347555 @default.
• W2589520828 cites W2010357110 @default.
• W2589520828 cites W2010373231 @default.
• W2589520828 cites W2010604165 @default.
• W2589520828 cites W2010904040 @default.
• W2589520828 cites W2014173031 @default.
• W2589520828 cites W2014336474 @default.
• W2589520828 cites W2019628762 @default.
• W2589520828 cites W2022628530 @default.
• W2589520828 cites W2026694261 @default.
• W2589520828 cites W2026792787 @default.
• W2589520828 cites W2027433526 @default.
• W2589520828 cites W2033731685 @default.
• W2589520828 cites W2034595898 @default.
• W2589520828 cites W2036037398 @default.
• W2589520828 cites W2037593826 @default.
• W2589520828 cites W2037839893 @default.
• W2589520828 cites W2041937465 @default.
• W2589520828 cites W2044775506 @default.
• W2589520828 cites W2044936883 @default.
• W2589520828 cites W2045195497 @default.
• W2589520828 cites W2046787882 @default.
• W2589520828 cites W2047157845 @default.
• W2589520828 cites W2050012719 @default.
• W2589520828 cites W2050650917 @default.
• W2589520828 cites W2051938152 @default.
• W2589520828 cites W2053826416 @default.
• W2589520828 cites W2054943797 @default.
• W2589520828 cites W2055527205 @default.
• W2589520828 cites W2055716317 @default.
• W2589520828 cites W2056521778 @default.
• W2589520828 cites W2058829106 @default.
• W2589520828 cites W2059117490 @default.
• W2589520828 cites W2059581034 @default.
• W2589520828 cites W2061225698 @default.
• W2589520828 cites W2062165317 @default.
• W2589520828 cites W2062756742 @default.
• W2589520828 cites W2064145632 @default.
• W2589520828 cites W2068293422 @default.
• W2589520828 cites W2072211596 @default.
• W2589520828 cites W2074829978 @default.
• W2589520828 cites W2076978913 @default.
• W2589520828 cites W2077687762 @default.
• W2589520828 cites W2078844308 @default.

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