
GPCR Biology
G-Protein Coupled Receptors (GPCRs) are one of the largest receptor families in the genome and are essential for the healthy function of nearly every organ in the body. GPCRs are also important targets for therapeutic drugs. Increase your understanding of drug effects and GPCR biology with bright fluorescent assays in living cells.
With our GPCR Assays in Living Cells, you can:
- Detect kinetic Gs, Gi, and Gq mediated responses in living cells
- Measure arrestin recruitment
- Combine multiple assays in the same cell population
- Express sensors and run assays in disease relevant cell types
- Detect fluorescence on imaging systems or automated plate readers (Z’ > 0.8)
- Quantify agonist bias
- De-orphanize receptors
Detecting β-Arrestin
Fluorescent Borealis arrestin assays to detect arrestin recruitment at specific GPCRs.
Measuring GPCR Signaling Kinetics
See the Assay Guidance Manual chapter from NIH NCATS:
Express GPCRs with BacMam
We have a growing catalog of GPCRs packaged in a modified Baculovirus vector, BacMam. BacMam transduction is a low-cost, effective method to express GPCRs in your cells of interest, including in primary and iPSC derived cells. See low cell-to-cell variability in expression, get consistent results from experiment to experiment, and titrate expression to your desired level. For more information and a current list of available receptors please see our GPCRs page.
Continuous Multiplex Measurements
Red fluorescent DAG sensor multiplexed with cADDis, a green fluorescent cAMP sensor, indicates Gs & Gq signaling via a calcitonin receptor.
Assays in Primary Cultures or iPSCs
Detect GPCR mediated responses in cells relevant to your disease, drug target, or biology of interest. Our BacMam-packaged sensors have been used in neurons, cardiomyoctes, islets, and many more primary and iPSC derived cells. Examples can be found on our Scientific Publications page. Alternate promoters or viral vectors are available by request. Pictured, at right, are the cADDis cAMP Assay in primary striatal neurons and the Red GECO calcium assay in nCardia’s Cor.4u cardiomyocytes.
Simple Protocol
We strive to create simple protocols with minimal liquid handling. Cell lysis, IBMX, enzymes, and co-factors are not necessary for these assays. Add our sensors to your cells, incubate, add drug, and measure fluorescent changes.
Read more on each of our specific GPCR Assays and receptors:
Shop Other Assay Kits by Category
Recent Publications
- ER McGlone, et al. Hepatocyte cholesterol content modulates glucagon receptor signaling. Molecular Metabolism. September 2022.
- B. Barsi-Rhyne, et al. Discrete GPCR-triggered endocytic modes enable β-arrestins to flexible regulate cell signaling. bioRxiv. July 2022.
- J. Xu, J. Pluznick. Key amino acids alter activity and trafficking of a well-conserved olfactory receptor. Cell Physiology. June 2022.
- C. Zhang, et al. A brainstem circuit for nausea suppression. Cell Reports. June 2022.
- J. Hansen, et al. A cAMP signalome in primary cilia drives gene expression and kidney cyst formation. EMBO Reports. June 2022.
- S. Ansari, et al. Morphogen Directed Coordination of GPCR Activity Promotes Primary Cilium Function for Downstream Signaling. bioRxiv. May 2022.
- E. Porpiglia, et al. Elevated CD47 is a hallmark of dysfunctional aged muscle stem cells that can be targeted to augment regeneration. bioRxiv. April 2022.
- S. Bitsi, et al. Divergent acute versus prolonged in vivo GLP-1R responses in β-arrestin 2-deleted primary beta cells. bioRxiv. April 2022.
- Y. Mizobuchi, et al. Ketamine Improves Desensitization of μ-Opioid Receptors Induced by Repeated Treatment with Fentanyl but Not with Morphine. biomolecules. March 2022.
- B. Polacco, et al. Profiling the diversity of agonist-selective effects on the proximal proteome environment of G protein-coupled receptors. bioRxiv. March 2022.
- D. Lovinger, et al. Local modulation by presynaptic receptors controls neuronal communication and behavior. Nature Reviews Neuroscience. February 2022.
- F. De Logu, et al. Schwann cell endosome CGRP signals elicit peri orbital mechanical allodynia in mice. Nature Communications. February 2022.
- A. Lutas, et al. History-dependent dopamine release increases cAMP levels in most basal amygdala glutamatergic neurons to control learning. Cell Reports. January 2022.
- G. Sancar, et al. FGF1 and insulin control lipolysis by convergent pathways. Cell Metabolism. January 2022.
- S. Hoare, et al. Quantifying the Kinetics of Signaling and Arrestin Recruitment by Nervous System G-Protein Coupled Receptors. Frontiers in Cellular Neuroscience. January 2022.
- J. H. Cho, et al. Islet primary cilia motility controls insulin secretion. bioRxiv. December 2021.
- Y. Karasawa, et al. In Vitro Analyses of Spinach-Derived Opioid Peptides, Rubiscolins: Receptor Selectivity and Intracellular Activities through G-protein- and β-arrestin-Mediated Pathways. Molecules. October 2021.
- A. White, et al. Spatial Bias in cAMP generation determines biological responses to PTH type 1 receptor activation. Science Signaling. October 2021.
- J. Janetzko, et al. Membrane phosphoinositides stabilize GPCR-arrestin complexes and offer temporal control of complex assembly and dynamics. bioRxiv. October 2021.
- S. Hoare, T. Hughes. Biosensor Assays for Measuring the Kinetics of G-Protein and Arrestin-Mediated Signaling in Live Cells. The Assay Guidance Manual. September 2021.
- M. Doepner, et al. Endogenous DOPA inhibits melanoma through suppression of CHRM1 signaling. Science Advances. September 2022.
- A. Kim, et al. Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes. eLife. November 2021. (bioRxiv)
- S. Hoare, T. Hughes. Biosensor Assays for Measuring the Kinetics of G-Protein and Arrestin-Mediated Signaling in Live Cells. The Assay Guidance Manual. September 2021.
- E. Maguire, et al. The Alzheimer's disease protective P522R variant of PLCG2, consistently enhances stimulus-dependent PLCγ2 activation, depleting substrate and altering cell function. bioRxiv. April 2020.
- L. Liu, et al. Diacylglycerol kinases regulate TRPV1 channel activity. Journal of Biological Chemistry. April 2020.
- S. Hoare, et al. A kinetic method for measuring agonist efficacy and ligand bias using high resolution biosensors and a kinetic data analysis framework. Nature Scientific Reports Feb 2020.
- C Deisl et al. Hypertrophy of human embryonic stem cell–derived cardiomyocytes supported by positive feedback between Ca2+ and diacylglycerol signals. Pflügers Archiv – European Journal of Physiology Jun. 2019
- Herranz, Gonzalo et al. Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells. Frontiers in Immunology Apr. 2019
- Ohno, et al. Dynamics of Presynaptic Diacylglycerol in a Sensory Neuron Encode Differences between Past and Current Stimulus Intensity. Cell Reports, Vol. 20, Issue 10. Sept. 2017
- Q. Wang, et al. Regulator of G protein signaling Gβ5-R7 is a crucial activator of muscarinic M3 receptor-stimulated insulin secretion. FASEB J. Jul. 7,2017.
- Shigeto, et al. GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation. J Clinical Invest. 2015. doi:10.1172/JCI81975.
- Xingjuan, et al. PKC-dependent Phosphorylation of the H1 Histamine Receptor Modulates TRPC6 Activity. Cells. 2014.
- P. Tewson, et al. New DAG and cAMP Sensors Optimized for Live-Cell Assays in Automated Laboratories. J Biomol Screen Dec. 2015. Request Full Text PDF
- Arttamangkul, et al.Does PKC activation increase the homologous desensitization of μ opioid receptors?British Journal of Pharmacology April 2014
- Tewson, et al. Simultaneous Detection of Ca2+and Diacylglycerol Signaling in Living Cells. PLoS One. 2012.
- L. Brueggemann, et al. Structural Determinants of Kv7.5 Potassium Channels that Confer Changes in Phosphatidylinositol 4,5-Biphosphate (PIP2) Affinity and Signaling Sensitivity in Smooth Muscle Cells. Molecular Pharmacology. March 2020.
- L.Liu, et al. Gαq sensitizes TRPM8 to inhibition by PI(4,5)P2 depletion upon receptor activation. J.Neurosci. May 2019.
- Teaching an Old Drug New Tricks: Agonism, Antagonism, and Biased Signaling of Pilocarpine through M3 Muscarinic Acetylcholine Receptor Molecular Pharmacology Nov. 2018 , and
- Y. Ding, et al. Ratiometric biosensors based on dimerization dependent fluorescent protein exchange. Nature Methods, 2015.
- P. Tewson, et al. A multiplexed fluorescent assay for independent second-messenger systems: decoding GPCR activation in living cells. J. Biomolecular Screening 18, 2013.
- M. Thomas, et al. Optically activated, customizable, excitable cells. PLOS One. December 2020.
- L. Liu, et al. Diacylglycerol kinases regulate TRPV1 channel activity. Journal of Biological Chemistry. April 2020.
- S. Hoare, et al. A kinetic method for measuring agonist efficacy and ligand bias using high resolution biosensors and a kinetic data analysis framework. Nature Scientific Reports Feb 2020.
- K. Harlen, et al. Live-Cell Assays for Cell Stress Responses Reveal New Patterns of Cell Signaling Caused by Mutations in Rhodopsin, α-Synuclein and TDP-43 Front. Cell. Neurosci.,December 2019
- M.C. Cañizal, et al. A Dual Ca2+/ DAG Sensor Reports on Ligand Efficiency.
- C. Xingjuan, et al. PKC-dependent Phosphorylation of the H1 Histamine Receptor Modulates TRPC6 Activity. Cells. 2014.
- P. Tewson, et al. A multiplexed fluorescent assay for independent second-messenger systems: decoding GPCR activation in living cells. Journal of Biomolecular Screening 18, 2013.
- J. Wu, et al. Improved Orange and Red Ca2+ Indicators and Photophysical Considerations for Optogenetic Applications. ACS Chem Neurosci. Jun. 19, 2013
- H.J. Carlson, et al. Mutational Analysis of a Red Fluorescent Protein-Based Calcium Ion Indicator. Sensors, 2013.
- P. Tewson, et al. Simultaneous Detection of Ca2+ and Diacylglycerol Signaling in Living Cells. PLoS One. 2012.
- H. Schiff, et al. β-arrestin-biased proteinase-activated receptor-2 antagonist C781 limits allergen-induced airway hyperresponsiveness and inflammation. British Journal of Pharmacology. June 2022.
- S. Hoare, et al. Quantifying the Kinetics of Signaling and Arrestin Recruitment by Nervous System G-Protein Coupled Receptors. Frontiers in Cellular Neuroscience. January 2022.
- S. Hoare, T. Hughes. Biosensor Assays for Measuring the Kinetics of G-Protein and Arrestin-Mediated Signaling in Live Cells. The Assay Guidance Manual. September 2021.
- S. Hoare, et al. Analyzing kinetic signaling data for G-protein-coupled receptors. Nature Scientific Reports. July 2020.
- S. Hoare, et al. A kinetic method for measuring agonist efficacy and ligand bias using high resolution biosensors and a kinetic data analysis framework. Nature Scientific Reports. Feb 2020.
- Characterizing GPCR Activaton using Live Cell Imaging. Biotek Instruments
- Real-Time Detection of Gs and Gi Signaling in Living Cells on a BMG CLARIOstar. BMG LabTech
- Simultaneous detection of GPCR second messengers in living cells. BMG LabTech
- Thapsigargin-induced Cellular Stress Response and Inhibition of Gq-dependent Calcium Signaling. Biotek Instruments