Molecular Mechanisms of Nicergoline from Ergot Fungus in Blocking Human 5-HT3A Receptor.

IF 2.5 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of microbiology and biotechnology Pub Date : 2024-11-29 DOI:10.4014/jmb.2411.11020
Minsu Pyeon, Myungmi Moon, Jeongyeon Yun, Jaehui Yang, Hye Duck Yeom, Gihyun Lee, Junho H Lee
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Abstract

This study investigates the modulatory effects of nicergoline, a major bioactive compound derived from ergot fungus, on the 5-hydroxytryptamine 3A (5-HT3A) receptor. Utilizing a two-electrode voltage-clamp technique, we evaluated the impact of nicergoline on the 5-HT-induced inward current (I5-HT) in 5-HT3A receptors. Our findings reveal that nicergoline inhibits I5-HT in a reversible and concentration-dependent manner. Additionally, the observed voltage-dependent and use-dependent inhibition indicates that nicergoline acts as an open channel blocker of the 5-HT3A receptor. To further elucidate the interaction between nicergoline and the 5-HT3A receptor, we conducted molecular docking studies. Overactivation of the 5-HT3A receptor can enhance excitatory neurotransmission, potentially leading to heightened anxiety and stress responses. It may also interfere with hippocampal functions, adversely affecting learning and memory. Additionally, exceed activation of these receptors is a primary mechanism underlying nausea and vomiting, commonly observed during chemotherapy or in response to certain toxins. Collectively, our results suggest that nicergoline has the potential to inhibit 5-HT3A receptor activity by interacting with binding residues L260 and V264. This inhibition may enhance cognitive function by stabilizing neural circuits involved in cognitive processes and can improve cognitive symptoms in patients with dementia. Additionally, the anxiolytic effects resulting from 5-HT3A receptor inhibition could promote overall psychological well-being in affected individuals. Thus, the role of nicergoline as a 5-HT3A receptor antagonist not only highlights its therapeutic potential but also warrants further exploration into its mechanisms and broader implications for managing neurodegenerative diseases.

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来源期刊
Journal of microbiology and biotechnology
Journal of microbiology and biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-MICROBIOLOGY
CiteScore
5.50
自引率
3.60%
发文量
151
审稿时长
2 months
期刊介绍: The Journal of Microbiology and Biotechnology (JMB) is a monthly international journal devoted to the advancement and dissemination of scientific knowledge pertaining to microbiology, biotechnology, and related academic disciplines. It covers various scientific and technological aspects of Molecular and Cellular Microbiology, Environmental Microbiology and Biotechnology, Food Biotechnology, and Biotechnology and Bioengineering (subcategories are listed below). Launched in March 1991, the JMB is published by the Korean Society for Microbiology and Biotechnology (KMB) and distributed worldwide.
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