Antimigraine Drug Avitriptan Is a Ligand and Agonist of Human Aryl Hydrocarbon Receptor that Induces CYP1A1 in Hepatic and Intestinal Cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F20%3A73601308" target="_blank" >RIV/61989592:15310/20:73601308 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1422-0067/21/8/2799/htm" target="_blank" >https://www.mdpi.com/1422-0067/21/8/2799/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21082799" target="_blank" >10.3390/ijms21082799</a>

Result language

angličtina

Original language name

Antimigraine Drug Avitriptan Is a Ligand and Agonist of Human Aryl Hydrocarbon Receptor that Induces CYP1A1 in Hepatic and Intestinal Cells

Original language description

The efforts for therapeutic targeting of the aryl hydrocarbon receptor (AhR) have emerged in recent years. We investigated the effects of available antimigraine triptan drugs, having an indole core in their structure, on AhR signaling in human hepatic and intestinal cells. Activation of AhR in reporter gene assays was observed for Avitriptan and to a lesser extent for Donitriptan, while other triptans were very weak or no activators of AhR. Using competitive binding assay and by homology docking, we identified Avitriptan as a low-affinity ligand of AhR. Avitriptan triggered nuclear translocation of AhR and increased binding of AhR in CYP1A1 promotor DNA, as revealed by immune-fluorescence microscopy and chromatin immune-precipitation assay, respectively. Strong induction of CYP1A1 mRNA was achieved by Avitriptan in wild type but not in AhR-knockout, immortalized human hepatocytes, implying that induction of CYP1A1 is AhR-dependent. Increased levels of CYP1A1 mRNA by Avitriptan were observed in human colon carcinoma cells LS180 but not in primary cultures of human hepatocytes. Collectively, we show that Avitriptan is a weak ligand and activator of human AhR, which induces the expression of CYP1A1 in a cell-type specific manner. Our data warrant the potential off-label therapeutic application of Avitriptan as an AhR-agonist drug.

Czech name

—

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

<a href="/en/project/NV19-05-00220" target="_blank" >NV19-05-00220: ACTIVATORS OF HUMAN ARYL HYDROCARBON RECEPTOR (AHR) IN THE THERAPY OF INFLAMMATORY BOWEL DISEASE</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

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

Name of the periodical

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

21

Issue of the periodical within the volume

8

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

"2799-1"-"2799-15"

UT code for WoS article

000535565300141

EID of the result in the Scopus database

2-s2.0-85083861173