G protein coupled receptors (GPCRs) are the largest group of membrane receptors. They transfer extracellular signals to intracellular G proteins and thereby regulate a variety of cellular responses. GPCRs are established drug targets while the direct modulation of G proteins is less well-characterized.

We are interested in GPCR- and G protein-dependent signaling mechanisms and their pharmacological modulation in blood vessels and airways. This should result in new drugs for the treatment of lung and heart diseases such as asthma, COPD, pulmonary hypertension and right heart failure.

The pharmacological pan-Gq inhibitor FR900359 (FR) relaxes airways ex and in vivo. Left: FR relaxes small intrapulmonary airways after pre-constriction with methacholine (MCh) in precision-cut lung slices of mouse. The graph displays the change of airway lumen area during the measurement, numbers indicate time-points during perfusion in the graph. Right: FR prevents the elevation of airway resistance (Rrs) by MCh in mouse in vivo, this effect is stronger than that of the well-established bronchodilator salbutamol. (Matthey et al. Targeted inhibition of Gq signaling induces airway relaxation in mouse models of asthma, Sci Transl Med, 2017)