All Outputs (59)

Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2 (2017)
Journal Article
Huma, Z. E., Sanchez, J., Lim, H. D., Bridgford, J. L., Huang, C., Parker, B. J., …Stone, M. J. (2017). Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2. Science Signaling, 10(480), Article eaai8529. https://doi.org/10.1126/scisignal.aai8529

Chemokines and their receptors collectively orchestrate the trafficking of leukocytes in normal immune function and inflammatory diseases. Different chemokines can induce distinct responses at the same receptor. In comparison to monocyte chemoattract... Read More about Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2.

Distribution and trafficking of the ?-opioid receptor in enteric neurons of the guinea pig (2016)
Journal Article
Lay, J., Carbone, S. E., DiCello, J. J., Bunnett, N. W., Canals, M., & Poole, D. P. (2016). Distribution and trafficking of the ?-opioid receptor in enteric neurons of the guinea pig. AJP - Gastrointestinal and Liver Physiology, 311(2), G252-G266. https://doi.org/10.1152/ajpgi.00184.2016

© 2016 the American Physiological Society. The μ-opioid receptor (MOR) is a major regulator of gastrointestinal motility and secretion and mediates opiate-induced bowel dysfunction. Although MOR is of physiological and therapeutic importance to gut f... Read More about Distribution and trafficking of the ?-opioid receptor in enteric neurons of the guinea pig.

Systematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor (2016)
Journal Article
Thompson, G., Lane, J., Coudrat, T., Sexton, P., Christopoulos, A., & Canals, M. (2016). Systematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor. Biochemical Pharmacology, 113, 70-87. https://doi.org/10.1016/j.bcp.2016.05.014

Biased agonism describes the ability of distinct G protein-coupled receptor (GPCR) ligands to stabilise distinct receptor conformations leading to the activation of different cell signalling pathways that can deliver different physiologic outcomes. T... Read More about Systematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor.

Protein kinase D and G?? subunits mediate agonist-evoked translocation of protease-activated receptor-2 from the golgi apparatus to the plasma membrane (2016)
Journal Article
Jensen, D. D., Zhao, P., Jimenez-Vargas, N. N., Lieu, T. M., Gerges, M., Yeatman, H. R., …Bunnett, N. W. (2016). Protein kinase D and Gβγ subunits mediate agonist-evoked translocation of protease-activated receptor-2 from the golgi apparatus to the plasma membrane. Journal of Biological Chemistry, 291(21), 11285-11299. https://doi.org/10.1074/jbc.M115.710681

Agonist-evoked endocytosis of G protein-coupled receptors has been extensively studied. The mechanisms by which agonists stimulate mobilization and plasma membrane translocation of G protein-coupled receptors from intracellular stores are unexplored.... Read More about Protein kinase D and G?? subunits mediate agonist-evoked translocation of protease-activated receptor-2 from the golgi apparatus to the plasma membrane.

The role of kinetic context in apparent biased agonism at GPCRs (2016)
Journal Article
Javitch, J. A., Klein Herenbrink, C., Sykes, D. A., Donthamsetti, P., Canals, M., Coudrat, T., …Lane, J. R. (2016). The role of kinetic context in apparent biased agonism at GPCRs. Nature Communications, 7, Article 10842. https://doi.org/10.1038/ncomms10842

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usu... Read More about The role of kinetic context in apparent biased agonism at GPCRs.

Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors (2016)
Journal Article
Shang, Y., Yeatman, H., Provasi, D., Alt, A., Christopoulos, A., Canals, M., & Filizola, M. (2016). Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors. ACS Chemical Biology, 11(5), 1220-1229. https://doi.org/10.1021/acschembio.5b00712

Available crystal structures of opioid receptors provide a high-resolution picture of ligand binding at the primary ("orthosteric") site, that is, the site targeted by endogenous ligands. Recently, positive allosteric modulators of opioid receptors h... Read More about Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors.

Plasma membrane localization of the μ-opioid receptor controls spatiotemporal signaling (2016)
Journal Article
Halls, M., Yeatman, H., Nowell, C., Thompson, G., Gondin, A., Civciristov, S., …Canals, M. (2016). Plasma membrane localization of the μ-opioid receptor controls spatiotemporal signaling. Science Signaling, 9(414), ra16-ra16. https://doi.org/10.1126/scisignal.aac9177

Differential regulation of the μ-opioid receptor (MOR), a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor, contributes to the clinically limiting effects of opioid analgesics, such as morphine. We used biophysical appro... Read More about Plasma membrane localization of the μ-opioid receptor controls spatiotemporal signaling.

Synthesis, Biological Evaluation, and Utility of Fluorescent Ligands Targeting the ?-Opioid Receptor (2015)
Journal Article
Schembri, L. S., Stoddart, L. A., Briddon, S. J., Kellam, B., Canals, M., Graham, B., & Scammells, P. J. (2015). Synthesis, Biological Evaluation, and Utility of Fluorescent Ligands Targeting the ?-Opioid Receptor. Journal of Medicinal Chemistry, 58(24), 9754-9767. https://doi.org/10.1021/acs.jmedchem.5b01664

Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on... Read More about Synthesis, Biological Evaluation, and Utility of Fluorescent Ligands Targeting the ?-Opioid Receptor.

The complex roles of ?-opioid receptor phosphorylation: A key determinant in receptor signaling and regulation (2015)
Journal Article
Canals, M. (2015). The complex roles of ?-opioid receptor phosphorylation: A key determinant in receptor signaling and regulation. Molecular Pharmacology, 88(4), 814-815. https://doi.org/10.1124/mol.115.100180

Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics. This Commentary focuses on two articles in the October 2015 issue of Molecular Pharmacology that investigate the role of μ-opioid receptor phosphorylation in rec... Read More about The complex roles of ?-opioid receptor phosphorylation: A key determinant in receptor signaling and regulation.

Biased Agonism of Endogenous Opioid Peptides at the ?-Opioid Receptor (2015)
Journal Article
Thompson, G. L., Lane, J. R., Coudrat, T., Sexton, P. M., Christopoulos, A., & Canals, M. (2015). Biased Agonism of Endogenous Opioid Peptides at the ?-Opioid Receptor. Molecular Pharmacology, 88(2), 335-346. https://doi.org/10.1124/mol.115.098848

Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics. Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate dif... Read More about Biased Agonism of Endogenous Opioid Peptides at the ?-Opioid Receptor.

Discovery, synthesis, and molecular pharmacology of selective positive allosteric modulators of the ?-opioid receptor (2015)
Journal Article
Burford, N. T., Livingston, K. E., Canals, M., Ryan, M. R., Budenholzer, L., Han, Y., …Alt, A. (2015). Discovery, synthesis, and molecular pharmacology of selective positive allosteric modulators of the δ-opioid receptor. Journal of Medicinal Chemistry, 58(10), 4220-4229. https://doi.org/10.1021/acs.jmedchem.5b00007

© 2015 American Chemical Society. Allosteric modulators of G protein-coupled receptors (GPCRs) have a number of potential advantages compared to agonists or antagonists that bind to the orthosteric site of the receptor. These include the potential fo... Read More about Discovery, synthesis, and molecular pharmacology of selective positive allosteric modulators of the ?-opioid receptor.

Detection and quantifi cation of intracellular signaling using fret-based biosensors and high content imaging (2015)
Book Chapter
Halls, M. L., Poole, D. P., Ellisdon, A. M., Nowell, C. J., & Canals, M. (2015). Detection and quantifi cation of intracellular signaling using fret-based biosensors and high content imaging. In G Protein-Coupled Receptors in Drug Discovery, (131-161). (2nd). Humana Press. https://doi.org/10.1007/978-1-4939-2914-6_10

© Springer Science+Business Media New York 2015. Förster resonance energy transfer (FRET) biosensors represent invaluable tools to detect the spatiotemporal context of second messenger production and intracellular signaling that cannot be attained us... Read More about Detection and quantifi cation of intracellular signaling using fret-based biosensors and high content imaging.

Detection and quantification of allosteric modulation of endogenous M4 muscarinic acetylcholine receptor using impedance-based label-free technology in a neuronal cell line (2014)
Journal Article
Chen, A. N., Chen, A., Malone, D. T., Pabreja, K., Sexton, P. M., Christopoulos, A., & Canals, M. (2014). Detection and quantification of allosteric modulation of endogenous M4 muscarinic acetylcholine receptor using impedance-based label-free technology in a neuronal cell line. Journal of Biomolecular Screening, 20(5), 646-654. https://doi.org/10.1177/1087057114563025

© 2014 Society for Laboratory Automation and Screening. Allosteric modulators of G protein-coupled receptors have the potential to achieve greater receptor subtype selectivity compared with ligands targeting the orthosteric site of this receptor fami... Read More about Detection and quantification of allosteric modulation of endogenous M4 muscarinic acetylcholine receptor using impedance-based label-free technology in a neuronal cell line.

Structural basis of receptor sulfotyrosine recognition by a cc chemokine: The n-terminal region of CCR3 bound to CCL11/eotaxin-1 (2014)
Journal Article
Millard, C. J., Ludeman, J. P., Canals, M., Bridgford, J. L., Hinds, M. G., Clayton, D. J., …Stone, M. J. (2014). Structural basis of receptor sulfotyrosine recognition by a cc chemokine: The n-terminal region of CCR3 bound to CCL11/eotaxin-1. Structure, 22(11), 1571-1581. https://doi.org/10.1016/j.str.2014.08.023

© 2014 Elsevier Ltd. Trafficking of leukocytes in immune surveillance and inflammatory responses is activated by chemokines engaging their receptors. Sulfation of tyrosine residues in peptides derived from the eosinophil chemokine receptor CCR3 drama... Read More about Structural basis of receptor sulfotyrosine recognition by a cc chemokine: The n-terminal region of CCR3 bound to CCL11/eotaxin-1.

Mechanistic Insights into Allosteric Structure-Function Relationships at the M1 Muscarinic Acetylcholine Receptor (2014)
Journal Article
Abdul-Ridha, A., Lane, J. R., Mistry, S. N., Lopez, L., Sexton, P. M., Scammells, P. J., …Canals, M. (2014). Mechanistic Insights into Allosteric Structure-Function Relationships at the M1 Muscarinic Acetylcholine Receptor. Journal of Biological Chemistry, 289(48), 33701-33711. https://doi.org/10.1074/jbc.m114.604967

Benzylquinolone carboxylic acid (BQCA) is the first highly selective positive allosteric modulator (PAM) for the M1 muscarinic acetylcholine receptor (mAChR), but it possesses low affinity for the allosteric site on the receptor. More recent drug dis... Read More about Mechanistic Insights into Allosteric Structure-Function Relationships at the M1 Muscarinic Acetylcholine Receptor.

Endothelin-converting enzyme 1 and ?-arrestins exert spatiotemporal control of substance P-induced inflammatory signals (2014)
Journal Article
Jensen, D. D., Halls, M. L., Murphy, J. E., Canals, M., Cattaruzza, F., Poole, D. P., …Bunnett, N. W. (2014). Endothelin-converting enzyme 1 and β-arrestins exert spatiotemporal control of substance P-induced inflammatory signals. Journal of Biological Chemistry, 289(29), 20283-20294. https://doi.org/10.1074/jbc.M114.578179

Although the intracellular trafficking of G protein-coupled receptors controls specific signaling events, it is unclear how the spatiotemporal control of signaling contributes to complex pathophysiological processes such as inflammation. By using bio... Read More about Endothelin-converting enzyme 1 and ?-arrestins exert spatiotemporal control of substance P-induced inflammatory signals.

Novel GPCR paradigms at the ?-opioid receptor (2014)
Journal Article
Thompson, G. L., Kelly, E., Christopoulos, A., & Canals, M. (2015). Novel GPCR paradigms at the ?-opioid receptor. British Journal of Pharmacology, 172(2), 287-296. https://doi.org/10.1111/bph.12600

© 2014 The British Pharmacological Society. Opioids, such as morphine, are the most clinically useful class of analgesic drugs for the treatment of acute and chronic pain. However, the use of opioids is greatly limited by the development of severe ad... Read More about Novel GPCR paradigms at the ?-opioid receptor.

Allosteric modulation of M1 muscarinic acetylcholine receptor internalization and subcellular trafficking (2014)
Journal Article
Yeatman, H. R., Lane, J. R., Choy, K. H. C., Lambert, N. A., Sexton, P. M., Christopoulos, A., & Canals, M. (2014). Allosteric modulation of M1 muscarinic acetylcholine receptor internalization and subcellular trafficking. Journal of Biological Chemistry, 289(22), 15856-15866. https://doi.org/10.1074/jbc.M113.536672

Background: The effects of allosteric modulators on G protein-coupled receptor trafficking are largely unknown. Results: The allosteric ligand BQCA modulates M1 mAChR arrestin recruitment and receptor trafficking. Conclusion: M1 mAChR trafficking is... Read More about Allosteric modulation of M1 muscarinic acetylcholine receptor internalization and subcellular trafficking.

Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor (2014)
Journal Article
Abdul-Ridha, A., López, L., Keov, P., Thal, D. M., Mistry, S. N., Sexton, P. M., …Christopoulos, A. (2014). Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor. Journal of Biological Chemistry, 289(9), 6067-6079. https://doi.org/10.1074/jbc.M113.539080

Benzylquinolone carboxylic acid (BQCA) is an unprecedented example of a selective positive allosteric modulator of acetylcholine at the M1 muscarinic acetylcholine receptor (mAChR). To probe the structural basis underlying its selectivity, we utilize... Read More about Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor.