Design, synthesis, and characterization of a novel fluoroprobe for live human islet cell imaging of serotonin 5-HT1A receptor

: 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 beta-cell insulin secretion. We report on 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-cells imaging. Compound 5a showed a 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.