Design, Synthesis, and Characterization of a Novel Fluoroprobe for Live Human Islet Cell Imaging of Serotonin 5‐HT1A Receptor

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‐HT 1A ) 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‐HT 1A receptor. The compounds were prepared by conjugating the scaffold of the 5‐HT 1A 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‐HT 1A receptor ( K i =1.8 nM). Fluoroprobe 5a was able to label the 5‐HT 1A receptor in pancreatic islet cell cultures in a selective manner, as the fluorescence emission was significantly attenuated by co‐administration of the 5‐HT 1A receptor antagonist WAY‐100635. Thus, fluoroprobe 5a showed useful properties to further characterize this unique receptor‘s role.