Nano‐analysis Reveals High Fraction of Serotonin Release during Exocytosis from a Gut Epithelium Model Cell

Electrochemical methods were used to explore the exocytotic nature of serotonin (5‐HT) release in human carcinoid BON cells, an in vitro human enterochromaffin cell model, to understand the mechanisms operating the release of gut‐derived 5‐HT in the intestinal mucosal epithelium. We show that the fractional vesicular 5‐HT release in BON cells is 80 % compared to previous work in pancreatic beta cells (34 %). The fractional release increased from 80 % in control BON cells to 87 % with 5‐HT preincubation and nearly 100 % with the combination of 5‐HT and the 5‐HT4 autoreceptor agonist, cisapride. Thus, partial release is the primary mechanism of exocytosis in BON cells, resulting in a variable amount of the vesicular content being released. Factors that control secretion of 5‐HT from enterochromaffin cells or BON cells are important as partial release provides a mechanism for development of effective therapeutic strategies to treat gastrointestinal diseases. Gut‐derived serotonin signaling plays key roles in the modulation of normal GI motility and inflammation. Electrochemical methods were used to study the release of serotonin during exocytosis in human carcinoid BON cells, which was found to be predominantly partial, with vesicles releasing a large fraction of serotonin during each exocytosis event. This finding provides new insights into therapeutic targets for treating GI diseases.