Design,Synthesis, and Characterization of a Novel Fluoroprobe for Live Human Islet Cell Imaging of Serotonin 5-HT1A Receptor |
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| Authors: | Robert W Garvey Prof Enza Lacivita Dr Mauro Niso Dr Beata Duszyńska Prof Paul E Harris Prof Marcello Leopoldo |
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| Affiliation: | 1. Division of Endocrinology, Department of Medicine and Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, NY 10033 USA;2. Dipartimento di Farmacia – Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy;3. Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland |
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| Abstract: | Mounting evidence suggests that the serotonin system serves in signal transmission to regulate insulin secretion in pancreatic islets of Langerhans. Among the 5-HT receptor subtype found in pancreatic islets, serotonin receptor 1A (5-HT1A) demonstrates a unique ability to inhibit β-cell insulin secretion. We report the design, synthesis, and characterization of two novel fluorescent probes for the 5-HT1A receptor. The compounds were prepared by conjugating the scaffold of the 5-HT1A receptor agonist 8-OH-DPAT with two fluorophores suitable for live-cell imaging. Compound 5a {5-(dimethylamino)-N-5-(8-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino]pentyl]naphtalen-1-sulfonammide} showed high affinity for the 5-HT1A receptor (Ki=1.8 nM). Fluoroprobe 5a was able to label the 5-HT1A receptor in pancreatic islet cell cultures in a selective manner, as the fluorescence emission was significantly attenuated by co-administration of the 5-HT1A receptor antagonist WAY-100635. Thus, fluoroprobe 5a showed useful properties to further characterize this unique receptor‘s role. |
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| Keywords: | serotonin serotonin 1A receptor fluorescent microscopy islets β-cells insulin vesicles diabetes |
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