Serotonin type 6 receptor inverse agonists and neutral antagonists inhibit defecation: relevance to intestinal motility disorders

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F25%3A73632452" target="_blank" >RIV/61989592:15310/25:73632452 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0014299925008532" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0014299925008532</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2025.178099" target="_blank" >10.1016/j.ejphar.2025.178099</a>

Result language

angličtina

Original language name

Serotonin type 6 receptor inverse agonists and neutral antagonists inhibit defecation: relevance to intestinal motility disorders

Original language description

The serotonergic system plays a crucial role in numerous physiological processes in the central and peripheral nervous systems. In the gastrointestinal (GI) tract, serotonin has been implicated in the control of motility and visceral pain associated with irritable bowel syndrome (IBS). Here, we investigated the impact of blocking differently activated conformational states of the type 6 serotonin receptor (5-HT6) upon intestinal motility and diarrhea in both non-stressed and stressed mice. We evaluated full and partial inverse agonists (SB-399885 and PZ-1444, respectively), which target constitutively active serotonin 5-HT6 receptors and a neutral antagonist (CPPQ), which targets agonist-activated serotonin 5-HT6 receptors. We found that both inverse agonists and the neutral antagonist, administered intraperitoneally at the same doses similarly reduce defecation in physiological and stressful conditions. The effect of PZ-1444 was significantly potentiated by the co-administration of either SB-399885 or CPPQ. CPPQ co-administration did not attenuate the effect of SB-399885 and this combination did not produce significantly stronger inhibition of defecation than SB-399885 administered alone. Combining PZ-1444 and CPPQ produced the most pronounced effect on defecation. The present findings confirm the contribution of both constitutively active and agoniststimulated serotonin 5-HT6 receptors to intestinal motility and diarrhea and highlights the serotonin 5-HT6 receptor as a promising drug target for the treatment of functional GI disorders.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

EUROPEAN JOURNAL OF PHARMACOLOGY

ISSN

0014-2999

e-ISSN

1879-0712

Volume of the periodical

1005

Issue of the periodical within the volume

OCT

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

6

Pages from-to

"178099-1"-"178099-6"

UT code for WoS article

001564576800008

EID of the result in the Scopus database

2-s2.0-105014393454