Imaging of Gα<sub>q</sub> Proteins in Mouse and Human Organs and Tissues
Jan H. Voss,
Haneen Al-Hroub,
Robin Gedschold,
Jennifer M. Dietrich,
Evelyn Gaffal,
Marieta Toma,
Stefan Kehraus,
Gabriele M. König,
Peter Brust,
Bernd K. Fleischmann,
Daniela Wenzel,
Winnie Deuther-Conrad,
Christa E. Müller
Affiliations
Jan H. Voss
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, D-53121 Bonn, Germany
Haneen Al-Hroub
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, D-53121 Bonn, Germany
Robin Gedschold
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, D-53121 Bonn, Germany
Jennifer M. Dietrich
Institute of Physiology I, Life & Brain Center, Medical Faculty, University of Bonn, D-53127 Bonn, Germany
Evelyn Gaffal
Department of Dermatology, University Hospital Magdeburg, D-39120 Magdeburg, Germany
Marieta Toma
Institute of Pathology, University Hospital Bonn (UKB), Medical Faculty, University of Bonn, D-53127 Bonn, Germany
Stefan Kehraus
Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, D-53115 Bonn, Germany
Gabriele M. König
Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, D-53115 Bonn, Germany
Peter Brust
Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, D-03418 Leipzig, Germany
Bernd K. Fleischmann
Institute of Physiology I, Life & Brain Center, Medical Faculty, University of Bonn, D-53127 Bonn, Germany
Daniela Wenzel
Institute of Physiology I, Life & Brain Center, Medical Faculty, University of Bonn, D-53127 Bonn, Germany
Winnie Deuther-Conrad
Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, D-03418 Leipzig, Germany
Christa E. Müller
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, D-53121 Bonn, Germany
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 Gαq 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 Gαq 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 Gαq 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 Gαq-protein-binding radio-tracers as novel diagnostics.
