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Imaging of Gα(q) Proteins in Mouse and Human Organs and Tissues

G protein-coupled receptors (GPCRs) transfer extracellular signals across cell membranes by activating intracellular heterotrimeric G proteins. Several studies suggested G proteins as novel drug targets for the treatment of complex diseases, e.g., asthma and cancer. Recently, we developed specific r...

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Autores principales: Voss, Jan H., Al-Hroub, Haneen, Gedschold, Robin, Dietrich, Jennifer M., Gaffal, Evelyn, Toma, Marieta, Kehraus, Stefan, König, Gabriele M., Brust, Peter, Fleischmann, Bernd K., Wenzel, Daniela, Deuther-Conrad, Winnie, Müller, Christa E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865079/
https://www.ncbi.nlm.nih.gov/pubmed/36678686
http://dx.doi.org/10.3390/pharmaceutics15010057
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author Voss, Jan H.
Al-Hroub, Haneen
Gedschold, Robin
Dietrich, Jennifer M.
Gaffal, Evelyn
Toma, Marieta
Kehraus, Stefan
König, Gabriele M.
Brust, Peter
Fleischmann, Bernd K.
Wenzel, Daniela
Deuther-Conrad, Winnie
Müller, Christa E.
author_facet Voss, Jan H.
Al-Hroub, Haneen
Gedschold, Robin
Dietrich, Jennifer M.
Gaffal, Evelyn
Toma, Marieta
Kehraus, Stefan
König, Gabriele M.
Brust, Peter
Fleischmann, Bernd K.
Wenzel, Daniela
Deuther-Conrad, Winnie
Müller, Christa E.
author_sort Voss, Jan H.
collection PubMed
description G protein-coupled receptors (GPCRs) transfer extracellular signals across cell membranes by activating intracellular heterotrimeric G proteins. Several studies suggested G proteins as novel drug targets for the treatment of complex diseases, e.g., asthma and cancer. Recently, we developed specific radiotracers, [³H]PSB-15900-FR and [³H]PSB-16254-YM, for the Gα(q) family of G proteins by tritiation of the macrocyclic natural products FR900359 (FR) and YM-254890 (YM). In the present study, we utilized these potent radioligands to perform autoradiography studies in tissues of healthy mice, mouse models of disease, and human tissues. Specific binding was high, while non-specific binding was extraordinarily low, giving nearly identical results for both radioligands. High expression levels of Gα(q) proteins were detected in healthy mouse organs showing the following rank order of potency: kidney > liver > brain > pancreas > lung > spleen, while expression in the heart was low. Organ sub-structures, e.g., of mouse brain and lung, were clearly distinguishable. Whereas an acute asthma model in mice did not result in altered Gα(q) protein expressions as compared to control animals, a cutaneous melanoma model displayed significantly increased expression in comparison to healthy skin. These results suggest the future development of Gα(q)-protein-binding radio-tracers as novel diagnostics.
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spelling pubmed-98650792023-01-22 Imaging of Gα(q) Proteins in Mouse and Human Organs and Tissues Voss, Jan H. Al-Hroub, Haneen Gedschold, Robin Dietrich, Jennifer M. Gaffal, Evelyn Toma, Marieta Kehraus, Stefan König, Gabriele M. Brust, Peter Fleischmann, Bernd K. Wenzel, Daniela Deuther-Conrad, Winnie Müller, Christa E. Pharmaceutics Article G protein-coupled receptors (GPCRs) transfer extracellular signals across cell membranes by activating intracellular heterotrimeric G proteins. Several studies suggested G proteins as novel drug targets for the treatment of complex diseases, e.g., asthma and cancer. Recently, we developed specific radiotracers, [³H]PSB-15900-FR and [³H]PSB-16254-YM, for the Gα(q) family of G proteins by tritiation of the macrocyclic natural products FR900359 (FR) and YM-254890 (YM). In the present study, we utilized these potent radioligands to perform autoradiography studies in tissues of healthy mice, mouse models of disease, and human tissues. Specific binding was high, while non-specific binding was extraordinarily low, giving nearly identical results for both radioligands. High expression levels of Gα(q) proteins were detected in healthy mouse organs showing the following rank order of potency: kidney > liver > brain > pancreas > lung > spleen, while expression in the heart was low. Organ sub-structures, e.g., of mouse brain and lung, were clearly distinguishable. Whereas an acute asthma model in mice did not result in altered Gα(q) protein expressions as compared to control animals, a cutaneous melanoma model displayed significantly increased expression in comparison to healthy skin. These results suggest the future development of Gα(q)-protein-binding radio-tracers as novel diagnostics. MDPI 2022-12-24 /pmc/articles/PMC9865079/ /pubmed/36678686 http://dx.doi.org/10.3390/pharmaceutics15010057 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Voss, Jan H.
Al-Hroub, Haneen
Gedschold, Robin
Dietrich, Jennifer M.
Gaffal, Evelyn
Toma, Marieta
Kehraus, Stefan
König, Gabriele M.
Brust, Peter
Fleischmann, Bernd K.
Wenzel, Daniela
Deuther-Conrad, Winnie
Müller, Christa E.
Imaging of Gα(q) Proteins in Mouse and Human Organs and Tissues
title Imaging of Gα(q) Proteins in Mouse and Human Organs and Tissues
title_full Imaging of Gα(q) Proteins in Mouse and Human Organs and Tissues
title_fullStr Imaging of Gα(q) Proteins in Mouse and Human Organs and Tissues
title_full_unstemmed Imaging of Gα(q) Proteins in Mouse and Human Organs and Tissues
title_short Imaging of Gα(q) Proteins in Mouse and Human Organs and Tissues
title_sort imaging of gα(q) proteins in mouse and human organs and tissues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865079/
https://www.ncbi.nlm.nih.gov/pubmed/36678686
http://dx.doi.org/10.3390/pharmaceutics15010057
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