Real-time monitoring norepinephrine exocytosis by high K+via an endoplasmic reticulum-targeting fluorescent probe

Abstract

Norepinephrine (NE), a neurotransmitter, has multiple functions in the neural system and peripheral organs. Abnormal levels of NE may lead to numerous neuro-degenerative and psychiatric disorders, such as Parkinson's disease, depression and Alzheimer's disease. Moreover, studies have indicated that an increase in NE may induce endoplasmic reticulum (ER) stress and cell apoptosis via oxidative stress. Therefore, developing a measure to monitor NE levels in the ER appears to be particularly important. The fluorescence imaging technique has become an ideal tool for detecting various biological molecules in situ, with the advantages of high selectivity, nondestructive testing, and real-time dynamic monitoring. However, there are currently no activatable ER fluorescent probes that can be used to monitor NE levels in the ER. Herein, a robust ER-targetable fluorescence probe (ER-NE) for detecting NE in the ER was constructed for the first time. With the excellent properties of high selectivity, low cytotoxicity and good biocompatibility for NE detection, ER-NE successfully achieved the detection of endogenous and exogenous NE under physiological conditions. More importantly, a probe was further applied to monitor NE exocytosis stimulated by continuous incubation with high K⁺. We expect that the probe may serve as a powerful tool for detecting NE and provide a potential new diagnostic method for related neurodegenerative diseases.