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• W2100093113 abstract "Recently, we reported the development of a species-specific neurotensin analog that displays selective binding affinity at the rat and human neurotensin (NT) receptor, L-[3,2′-Nal11]NT(8–13) (where Nal is naphthylalanine) (NT19). We have developed another neurotensin analog, L-[3,1′-Nal11]NT(8–13), (NT34), that exhibits a 126-fold difference in binding affinities between the rat and human receptors. This compound differs from our previous reported species-specific ligand in the steric positioning of the naphthyl ring on the L-alanine side chain. For NT34, the observed Kd values at the rat and human neurotensin receptors were 0.046 and 5.8 nM, respectively. In stimulating phosphatidylinositol turnover, the observed EC50 values were 2.8 nM and 130 nM in rat and human, respectively. We constructed a series of chimeric rat/human neurotensin receptor genes and expressed them by transient transfection into human embryonic kidney (HEK-293) cells. Radioligand binding assays were then performed using neurotensin and NT34. Our results led us to propose a region of the neurotensin receptor that may be involved in determining species specificity, i.e. the transmembrane VI, the third extracellular loop, and transmembrane VII regions of the neurotensin receptor. Recently, we reported the development of a species-specific neurotensin analog that displays selective binding affinity at the rat and human neurotensin (NT) receptor, L-[3,2′-Nal11]NT(8–13) (where Nal is naphthylalanine) (NT19). We have developed another neurotensin analog, L-[3,1′-Nal11]NT(8–13), (NT34), that exhibits a 126-fold difference in binding affinities between the rat and human receptors. This compound differs from our previous reported species-specific ligand in the steric positioning of the naphthyl ring on the L-alanine side chain. For NT34, the observed Kd values at the rat and human neurotensin receptors were 0.046 and 5.8 nM, respectively. In stimulating phosphatidylinositol turnover, the observed EC50 values were 2.8 nM and 130 nM in rat and human, respectively. We constructed a series of chimeric rat/human neurotensin receptor genes and expressed them by transient transfection into human embryonic kidney (HEK-293) cells. Radioligand binding assays were then performed using neurotensin and NT34. Our results led us to propose a region of the neurotensin receptor that may be involved in determining species specificity, i.e. the transmembrane VI, the third extracellular loop, and transmembrane VII regions of the neurotensin receptor. Chimeric rat/human neurotensin receptors localize a region of the receptor sensitive to binding of a novel, species-specific picomolar affinity peptideJournal of Biological ChemistryVol. 271Issue 36PreviewVol. 271, p. 15054 Full-Text PDF Open Access" @default.
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• W2100093113 date "1996-06-01" @default.
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• W2100093113 title "Chimeric Rat/Human Neurotensin Receptors Localize a Region of the Receptor Sensitive to Binding of a Novel, Species-specific, Picomolar Affinity Peptide" @default.
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• W2100093113 doi "https://doi.org/10.1074/jbc.271.25.15054" @default.
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