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GPCR-mediated signaling

Monitoring Functional Activation of Gs and Gi Subtypes 

Pre-treatment of β2 AR with selective Gs and Gi inhibitors cholera toxin (CTX)and pertussis toxin (PTX), respectively, modulates the kinetic impedance profi le of β2 AR selective agonist isoproterenol (ISO). Impedance encapsulates a holistic readout that captures the contribution of multiple G protein dependent signaling events to a cellular response. The rapid drop in cell index is delayed and reduced by PTX and to a lesser extent CTX, while both treatments largely block the longer term increase in cell index, indicating differential involvement of Gs and Gi signaling. (Data and figures adapted from Stallert W, et. al., 2012) 


Assessment of Gβγ -dependent Signaling

Inhibition of Gβγ-dependent signaling with gallein (Gall) demonstrates a reduced kinetic ISO-promoted impedance response. A slower ascending phase and partially decreased maximum response suggest a distinct role for Gβγ-dependent signaling. (Data and figures adapted from Stallert W, et. al., 2012) 


SELECT Publications for GPCR-Mediated Cell Signaling 

1.Label-free impedance responses of endogenous and synthetic chemokine receptor CXCR3 agonists correlate with Gi-protein pathway activation. 
Anne O. Watts, Danny J. Scholten, Laura H. Heitman, Henry F. Vischer, and Rob Leurs. 
Biochemical and Biophysical Research Communications. 9 Mar 2012;419(2):423-8. 

2.Impedance responses reveal β2 -adrenergic receptor signaling pluridimensionality and allow classification of ligands with distinct signaling profiles. 
Wayne Stallert, Jonas F. Dorn, Emma van der Westhuizen, Martin Audet, Michel Bouvier. 
PLoS One. 5 Jan 2012;7(1):e29420. DOI:10.1371/journal.pone.0029420. 

3.Impedance measurement: A new method to detect ligand-biased receptor signaling. 
M. Kammermann, A. Denelavas, A. Imbach, U. Grether, H. Dehmlow, C.M. Apfel, C. Hertel. 
 Biochemical and Biophysical Research Communications. 9 Jul 2011;412:419-424. 

4.Neurokinin 1 receptor mediates nembrane blebbing in HEK293 cells through a Rho/Rho-associated coiled-coil kinase-dependent mechanism. 
Meshki J, Douglas SD, Lai JP, Schwartz L, Kilpatrick LE, Tuluc F. 
The Journal of Biological Chemistry. 3 Apr 2009;284(14):9280-9. 

5.Real-time monitoring of morphological changes in living cells by electronic cell sensor arrays: an approach to study G protein coupled receptors. 
Yu N, Atienza JM, Bernard J, Blanc S, Zhu J, Wang X, Xu X, Abassi YA. 
Analytical Chemistry. 2006;78:35-43. 

Key Benefits 

• Simultaneous screening for GPCR function across all coupling classes: Gs, Gi, Gq, G12/13.
• Detection of traditionally difficult classes: Gand G12/13.
• Detection of functional selectivity.
• Potential advantage to de-orphaning of GPCRs.
• Assay endogenous GPCRs with primary cells, stem cells, and/or other disease relevant cells.