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.
Combine our red and green sensors in the same cells to measure multiple analytes simultaneously. Simply add both sensors to the transduction mix. Measure two signals, examine ligand bias, deorphanize GPCRs, and look for off-target GPCR activation.
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
GPCR Assay References
Borealis Arrestin Assay References
- 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.
cADDis cAMP Assay References
- B. Polacco, et al. Profiling the proximal proteome of the activated μ-opioid receptor. nature chemical biology. March 2024.
- P. Balraj, et al. Kisspeptin/KISS1R Signaling Modulates Human Airway Smooth Muscle Cell Migration. American Journal of Respiratory Cell and Molecular Biology. March 2024.
- J. Xu, et al. An evolutionarily conserved olfactory receptor is required for sex differences in blood pressure. Science Advances. March 2024 (bioRxiv)
- J. Alvarado et al. Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial neurons to suppress feeding. Neuron. February 2024. (bioRxiv)
- H. Hamzeh, et al. Deciphering rapid cell signaling and control of cell motility by reverse opto-chemical engineering. bioRxiv. February 2024.
- N. Philip. Fatty acid metabolism promotes TRPV4 activity in lung microvascular endothelial cells in pulmonary arterial hypertension. Lung Cellular and Molecular Physiology. January 2024.
- X. Chen, et al. A PACAP-activated network for secretion requires coordination of Ca2+ influx and Ca2+ mobilization. bioRxiv. January 2024.
- L. Ripoll & M. von Zastrow. Spatial organization of adenylyl cyclase and its impact on dopamine signaling in neurons. bioRxiv. December 2023.
- T. Richardson, Y. Pettway, et al. Human Pseudoislet System for Synchronous Assessment of Fluorescent Biosensor Dynamics and Hormone Secretory Profiles. Journal of Visualized Experiments. November 2023.
- C. Hinds, et al. Abolishing β-arrestin recruitment is necessary for the full metabolic benefits of G protein-biased glucagon-like peptide-1 receptor agonists. Diabetes, Obesity and Metabolism. October 2023.
- E. Blythe & M. von Zastrow. β-Arrestin-
independent endosomal cAMP signaling by a polypeptide hormone GPCR. Nature Chemical Biology. September 2023. - R. Matt, et al. Fingerprinting heterocellular β-adrenoceptor functional expression in the brain using agonist activity profiles. Frontiers in Molecular Biosciences. August 2023.
- Y. Kunioku, et al. Intracellular cAMP Signaling Pathway via Gs Protein-Coupled Receptor Activation in Rat Primary Cultured Trigeminal Ganglion Cells. Biomedicines. August 2023.
- K.M. Semesta, et al. The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction. Journal of Biological Chemistry. August 2023.
- Y.J. Peng, et al. Hypoxia sensing requires H2S-dependent persulfidation of olfactory receptor 78. Science Advances. July 2023.
- S. Zhang, et al. Competition between stochastic neuropeptide signals calibrates the rate of satiation. bioRxiv. July 2023.
- E. Kitayama, et al. Functional Expression of IP, 5-HT4, D1, A2A, and VIP Receptors in Human Odontoblast Cell Line. Biomolecules. May 2023.
- D. Santana Nunez, et al. Piezo1 induces endothelial responses to shear stress via soluble adenylyl Cyclase-IP3R2 circuit. iScience. May 2023.
- S. Bitsi, et al. Divergent acute versus prolonged pharmacological GLP-1R responses in adult β cell–specific β-arrestin 2 knockout mice. Science Advances. May 2023.
- V. Bhatia, et al. Characterization of Adenylyl Cyclase Isoform 6 Residues Interacting with Forskolin. Biology. April 2023.
- H. Carr, et al. The Wnt pathway protein Dvl1 targets Somatostatin receptor 2 for lysosome-dependent degradation. Journal of Biological Chemistry. March 2023.
- I. Cattani-Cavalieri, et al. Quantitative phosphoproteomic analysis reveals unique cAMP signaling pools emanating from AC2 and AC6 in human airway smooth muscle cells. Frontiers in Physiology. February 2023.
- E. Porpiglia, et al. Elevated CD47 is a hallmark of dysfunctional aged muscle stem cells that can be targeted to augment regeneration. Cell Stem Cell. December 2022. (bioRxiv)
- J. Janetzko, et al. Membrane phosphoinositides regulate GPCR-β-arrestin complex assembly and dynamics. Cell. November 2022.
- N. Saito, et al. Gαs-Coupled CGRP Receptor Signaling Axis from the Trigeminal Ganglion Neuron to Odontoblast Negatively Regulates Dentin Mineralization. biomolecules. November 2022.
- B. Barsi-Rhyne, et al. Discrete GPCR-triggered endocytic modes enable β-arrestins to flexibly regulate cell signaling. eLife. October 2022. (bioRxiv)
- S. A. Dai, et al. State-selective modulation of heterotrimeric Gαs signaling with macrocyclic peptides. Cell. September 2022.
- J. H. Cho, et al. Islet primary cilia motility controls insulin secretion. Science Advances. September 2022. (bioRxiv)
- E. Blythe, M. von Zastrow. A discrete mode of endosomal GPCR signaling that does not require β-arrestins. bioRxiv. September 2022.
- ER McGlone, et al. Hepatocyte cholesterol content modulates glucagon receptor signaling. Molecular Metabolism. September 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 signalosome 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.
- 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.
DAG Assay References
- X. Chen, et al. A PACAP-activated network for secretion requires coordination of Ca2+ influx and Ca2+ mobilization. bioRxiv. January 2024.
- Z. Miller, et al. Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14. Cell Reports. November 2023. (bioRxiv)
- N. Zaïmia, et al. GLP-1 and GIP receptors signal through distinct β-arrestin 2-dependent pathways to regulate pancreatic β cell function. Cell Reports. October 2023.
- G. Sanchez, et al. Coincident Regulation of PLCβ Signaling by Gq-Coupled and μ-Opioid Receptors Opposes Opioid-Mediated Antinociception. Molecular Pharmacology. December 2022.
- 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.
PIP2 Assay References
- 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.
GECO Calcium Assay References
- X. Chen, et al. A PACAP-activated network for secretion requires coordination of Ca2+ influx and Ca2+ mobilization. bioRxiv. January 2024.
- C. Amos, et al. Membrane lipids couple synaptotagmin to SNARE-mediated granule fusion in insulin-secreting cells. Molecular Biology of the Cell. December 2023.
- J. Wu, et al. Interaction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability and Working Memory. bioRxiv. March 2023.
- 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.
