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Last update 23 Jan 2025

5-HT5A receptor

Last update 23 Jan 2025

Basic Info

Synonyms

5-HT-5, 5-HT-5A, 5-HT5A

+ [5]

Introduction

This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins.

Drugs associated with 5-HT5A receptor

UCSF678

Target

5-HT5A receptor

Mechanism

5-HT5A receptor antagonists

Active Org.

The University of California, San Francisco

Originator Org.

The University of California, San Francisco

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SB-699551-A

Target

5-HT5A receptor

Mechanism

5-HT5A receptor antagonists

Active Org.

GlaxoSmithKline, Inc.

Originator Org.

GlaxoSmithKline, Inc.

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

5-HT5A receptor modulators(Virginia Commonwealth University)

Target

5-HT5A receptor

Mechanism

5-HT5A receptor modulators

Active Org.

Virginia Commonwealth University

Originator Org.

Virginia Commonwealth University

Active Indication

Central Nervous System Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with 5-HT5A receptor

100 Translational Medicine associated with 5-HT5A receptor

0 Patents (Medical) associated with 5-HT5A receptor

15,019

Literatures (Medical) associated with 5-HT5A receptor

31 Dec 2025·Gut Microbes

Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila

Article

Author: Wang, Huijing ; Fu, Mengwei ; Wang, Boyu ; Zhao, Xinyi ; Zhao, Chao ; Wang, Tongyao ; Ying, Yueming ; Yeerken, Anaguli ; Wei, Yuhuan ; Wu, Yuchen ; Shao, Chunhai ; Huo, Shaoye ; Wang, Lihong ; Qian, Chenglang ; Yang, Hao ; Pan, Miaomiao ; Zhao, Yunhua

The gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as a key mediator. However, it remains unclear whether specific microbial factors regulate tryptophan metabolism to influence 5-HT production and anxiety regulation. In this study, we analyzed 110 athletes undergoing closed training and found that fecal lactate levels were significantly associated with anxiety indicators. We observed a significant negative correlation between Akkermansia abundance and anxiety levels in athletes. Co-supplementation with lactate and Akkermansia muciniphila (A. muciniphila) modulated tryptophan metabolism by increasing key enzyme TPH1 and reducing IDO1, thus shifting metabolism from kynurenine (Kyn) to 5-HT. In addition, lactate enhanced the propionate production capacity of A. muciniphila, potentially contributing to anxiety reduction in mice. Taken together, these findings suggest that enteric lactate and A. muciniphila collaboratively restore the imbalance in tryptophan metabolism, leading to increased 5-HT activity and alleviating anxiety phenotypes. This study highlights the intricate interplay between gut metabolites and anxiety regulation, offering potential avenues for microbiota-targeted therapeutic strategies for anxiety.

01 Apr 2025·Archives of Medical Research

Membrane vesicles from lactobacillus acidophilus reduce intestinal inflammation and increase 5-HT in the substantia nigra of rats with parkinson's disease

Article

Author: Hesampour, Ardeshir ; Sheikh, Khadijeh ; Arasteh, Javad ; Tajabadi Ebrahimi, Maryam

BACKGROUNDThis study aimed to investigate the role of membrane vesicles (MVs) from the probiotic Lactobacillus acidophilus in reducing intestinal inflammation and increasing 5-hydroxytryptamine (5-HT) and tyrosine hydroxylase (TH) in the substantia nigra in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD).METHODSTwenty healthy male Wistar rats were randomly assigned to four groups (n = 5 per group), including a) control, b) 6-OHDA, c) 6-OHDA+MV, and d) sham groups. PD was induced by bilateral injection of 6-OHDA. Rats in the 6-OHDA+MV group received MV equivalent to 1 × 10⁷ colony-forming units (CFU)/mL 3 d/wk by oral gavage for 4 wk. At the end of 4 wk, all rats were sacrificed; the brain and small intestine were removed for cellular and molecular analysis.RESULTSThe induction of PD by 6-OHDA induced a remarkable decrease in beam-walking (p < 0.0001). In addition, the expression of protein and genes (receptor) of 5-HT (r-5-HT1A) decreased, and that of protein and gene (receptor; GABBR1) of GABA increased in the PD group (p < 0.05 compared with the healthy control group), while MV gavage of 6-OHDA-injected rats controlled these factors in the substantia nigra. In the intestinal tissue, the expression of TLR-4 and α-synuclein gene was significantly increased in the 6-OHDA group compared to the control group (p < 0.0001).CONCLUSIONMVs might act as potential beneficial tools to reduce intestinal inflammation, control neurological damage associated with PD, and increase 5-HT neurotransmitters. It seems that MVs from L. acidophilus may have therapeutic potential in Parkinson's neurological disorder by controlling the gut-brain axis.

01 Mar 2025·Biosensors and Bioelectronics

Programming a bacterial biosensor for directed evolution of tryptophan hydroxylase via high-throughput droplet sorting

Article

Author: Han, Yuying ; Lu, Fuping ; Tang, Guangyao ; Zhang, Wei ; Li, Huimin ; Qin, Hui-Min

The modification of tryptophan hydroxylase (TPH) for the biosynthesis of 5-hydroxytryptophan (5-HTP) has recently become a focus of research. In this study, we established a droplet-based ultrahigh-throughput microfluidic screening platform (DTSP) to improve the industrial properties of TPH, whereas a bacterial biosensor for L-tryptophan (L-Trp) detection was engineered to improve sensitivity. The promoter pJ23111 achieved a strong negative correlation between the L-Trp concentration and the fluorescence output of the biosensor. The optimized DTSP platform was then utilized to screen superior TPH mutants by employing iterative saturation mutagenesis (ISM). The M4-1 variant (D129L/Q132M/P103A/T236K) demonstrated a 4.25-fold increase of catalytic activity compared to the parental CviPAH. Moreover, it exhibited excellent thermostability, with a 3.2-fold increase of half-life at 45 °C. Our study provides a reference for the development of bacterial biosensors for microdroplet-based screening platforms.

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