5-hydroxytryptamine (5-HT) signaling pathway (5-HT signaling pathway)

The 5-hydroxytryptamine (5-HT) signaling pathway, commonly known as the serotonin signaling pathway, is a comprehensive biological system centered on the monoamine neurotransmitter serotonin, which acts as a key messenger in both the central nervous system (CNS) and the periphery (Jiang et al., 2021). It is primarily involved in regulating physiological processes such as mood, sleep, appetite, cognition, and gastrointestinal motility through a complex network of synthesis enzymes like tryptophan hydroxylase, transporters such as SERT, and a diverse array of receptor subtypes ranging from 5-HT1 to 5-HT7 (He et al., 2022). In the brain, 5-HT signaling is essential for emotional balance and stress response, while in the gut, it serves as a critical mediator of the brain-gut axis, influencing sensory and motor functions (Jiang et al., 2021). Dysregulation of this pathway is linked to major neuropsychiatric conditions like depression and anxiety, as well as functional gastrointestinal disorders like irritable bowel syndrome (IBS) and functional dyspepsia (Choi et al., 2023). Because of its pervasive roles, components of this pathway are among the most common therapeutic targets, including SSRIs for mood disorders, triptans for migraines, and 5-HT3 antagonists for nausea (Wu et al., 2023). Due to its systemic distribution, drugs affecting this pathway must be carefully managed to avoid complications such as serotonin syndrome or significant gastrointestinal side effects (Stasi et al., 2014).

Other names

Serotonin signaling pathwaySerotonergic signaling pathway5-HT pathwaySerotonin system5-hydroxytryptamine pathway

Drugs modulate this pathway through various mechanisms including the inhibition of the serotonin transporter (SERT) to increase synaptic 5-HT levels, the direct activation or inhibition of specific 5-HT receptor subtypes, and the inhibition of metabolic enzymes like monoamine oxidase.