Imaging of Gαq proteins in mouse and human organs and tissues


Imaging of Gαq proteins in mouse and human organs and tissues

Voss, J. H.; Al-Hroub, H.; Gedschold, R.; Dietrich, J.; Gaffal, E.; Toma, M.; Kehraus, S.; König, G. M.; Brust, P.; Fleischmann, B. K.; Wenzel, D.; Deuther-Conrad, W.; Müller, C. E.

G protein-coupled receptors (GPCRs) transfer extracellular signals across cell membranes by ac-tivating intracellular heterotrimeric G proteins. Recent studies suggested G proteins as novel drug targets for the treatment of complex diseases, e.g. asthma and cancer. Recently, we devel-oped 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 FR900259 (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, both radioligands giving nearly identical results. High expression levels of Gq proteins were detected in healthy mouse organs showing the following rank order of potency: kidney > liver > brain > pancreas > lung > spleen >> heart. Organ sub-structures, e.g. of mouse brain and lung, were clearly distinguishable. Whereas an acute asthma model in mouse did not result in altered Gq protein expression 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 Gq-protein-binding radiotracers as novel diagnostics.

Keywords: asthma; autoradiography; G protein-coupled receptors; Gαq protein; FR900359; mouse brain; YM-254890; radioligand; lung

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Publ.-Id: 35666