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Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications
Angiotensin II receptor blockers (ARBs) are one of the most frequently recommended antihypertensive drugs. Apart from their activity towards the circulatory system, ARBs also penetrate the blood-brain barrier and display neuroprotective effects. Kynurenic acid (KYNA) is an endogenous metabolite of t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602025/ https://www.ncbi.nlm.nih.gov/pubmed/28733707 http://dx.doi.org/10.1007/s12640-017-9781-2 |
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author | Zakrocka, Izabela Targowska-Duda, Katarzyna M. Wnorowski, Artur Kocki, Tomasz Jóźwiak, Krzysztof Turski, Waldemar A. |
author_facet | Zakrocka, Izabela Targowska-Duda, Katarzyna M. Wnorowski, Artur Kocki, Tomasz Jóźwiak, Krzysztof Turski, Waldemar A. |
author_sort | Zakrocka, Izabela |
collection | PubMed |
description | Angiotensin II receptor blockers (ARBs) are one of the most frequently recommended antihypertensive drugs. Apart from their activity towards the circulatory system, ARBs also penetrate the blood-brain barrier and display neuroprotective effects. Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan produced by kynurenine aminotransferase II (KAT II) in the brain. Antagonism towards all ionotropic glutamate (GLU) receptors is the main mechanism of KYNA action. An elevated brain level of KYNA is linked with memory impairment and psychotic symptoms. The aim of this study was to examine the influence of three ARBs: irbesartan, losartan, and telmisartan on KYNA production and KAT II activity in rat brain. The effect of ARBs on KYNA production was analyzed in rat brain cortical slices and on isolated KAT II enzyme. Irbesartan, losartan, and telmisartan decreased KYNA production and KAT II activity in a dose-dependent manner in rat brain cortex in vitro. Molecular docking suggested that the examined ARBs could bind to an active site of KAT II. In conclusion, ARBs decrease KYNA production in rat brain by direct inhibition of KAT II enzymatic activity. This novel mechanism of ARBs action may be advantageous in the treatment of cognitive impairment or the management of schizophrenia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12640-017-9781-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5602025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-56020252017-10-03 Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications Zakrocka, Izabela Targowska-Duda, Katarzyna M. Wnorowski, Artur Kocki, Tomasz Jóźwiak, Krzysztof Turski, Waldemar A. Neurotox Res Original Article Angiotensin II receptor blockers (ARBs) are one of the most frequently recommended antihypertensive drugs. Apart from their activity towards the circulatory system, ARBs also penetrate the blood-brain barrier and display neuroprotective effects. Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan produced by kynurenine aminotransferase II (KAT II) in the brain. Antagonism towards all ionotropic glutamate (GLU) receptors is the main mechanism of KYNA action. An elevated brain level of KYNA is linked with memory impairment and psychotic symptoms. The aim of this study was to examine the influence of three ARBs: irbesartan, losartan, and telmisartan on KYNA production and KAT II activity in rat brain. The effect of ARBs on KYNA production was analyzed in rat brain cortical slices and on isolated KAT II enzyme. Irbesartan, losartan, and telmisartan decreased KYNA production and KAT II activity in a dose-dependent manner in rat brain cortex in vitro. Molecular docking suggested that the examined ARBs could bind to an active site of KAT II. In conclusion, ARBs decrease KYNA production in rat brain by direct inhibition of KAT II enzymatic activity. This novel mechanism of ARBs action may be advantageous in the treatment of cognitive impairment or the management of schizophrenia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12640-017-9781-2) contains supplementary material, which is available to authorized users. Springer US 2017-07-21 2017 /pmc/articles/PMC5602025/ /pubmed/28733707 http://dx.doi.org/10.1007/s12640-017-9781-2 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Article Zakrocka, Izabela Targowska-Duda, Katarzyna M. Wnorowski, Artur Kocki, Tomasz Jóźwiak, Krzysztof Turski, Waldemar A. Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications |
title | Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications |
title_full | Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications |
title_fullStr | Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications |
title_full_unstemmed | Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications |
title_short | Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications |
title_sort | angiotensin ii type 1 receptor blockers inhibit kat ii activity in the brain—its possible clinical applications |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602025/ https://www.ncbi.nlm.nih.gov/pubmed/28733707 http://dx.doi.org/10.1007/s12640-017-9781-2 |
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