All Outputs (9)

Positive allosteric modulation of endogenous delta opioid receptor signaling in the enteric nervous system is a potential treatment for gastrointestinal motility disorders (2021)
Journal Article
DiCello, J. J., Carbone, S. E., Saito, A., Pham, V., Szymaszkiewicz, A., Gondin, A. B., …Poole, D. P. (2022). Positive allosteric modulation of endogenous delta opioid receptor signaling in the enteric nervous system is a potential treatment for gastrointestinal motility disorders. AJP - Gastrointestinal and Liver Physiology, 322(1), G66-G78. https://doi.org/10.1152/AJPGI.00297.2021

Allosteric modulators (AMs) are molecules that can fine-tune signaling by G protein-coupled receptors (GPCRs). Although they are a promising therapeutic approach for treating a range of disorders, allosteric modulation of GPCRs in the context of the... Read More about Positive allosteric modulation of endogenous delta opioid receptor signaling in the enteric nervous system is a potential treatment for gastrointestinal motility disorders.

Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia (2021)
Journal Article
Lillywhite, A., Woodhams, S. G., Gonçalves, S. V., Watson, D. J. G., Li, L., Burston, J. J., …Chapman, V. (2021). Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia. PAIN Reports, 6(4), Article e956. https://doi.org/10.1097/PR9.0000000000000956

Introduction: Negative affect, including anxiety and depression, is prevalent in chronic pain states such as osteoarthritis (OA) and associated with greater use of opioid analgesics, potentially contributing to present and future opioid crises.... Read More about Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia.

Atypical opioid receptors: unconventional biology and therapeutic opportunities (2021)
Journal Article
Palmer, C. B., Meyrath, M., Canals, M., Kostenis, E., Chevigné, A., & Szpakowska, M. (2022). Atypical opioid receptors: unconventional biology and therapeutic opportunities. Pharmacology and Therapeutics, Article 108014. https://doi.org/10.1016/j.pharmthera.2021.108014

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating four opioid receptors, namely μ (mu, MOP), δ (delta, DOP), κ (kappa, KOP) and the nociceptin/orphanin FQ receptor (NOP). Interestingly, several o... Read More about Atypical opioid receptors: unconventional biology and therapeutic opportunities.

Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology (2021)
Journal Article
Hill, R., & Canals, M. (2022). Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology. Pharmacology and Therapeutics, 230, Article 107961. https://doi.org/10.1016/j.pharmthera.2021.107961

Morphine and other mu-opioid receptor (MOR) agonists remain the mainstay treatment of acute and prolonged pain states worldwide. The major limiting factor for continued use of these current opioids is the high incidence of side effects that result in... Read More about Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology.

Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management (2021)
Journal Article
Bonifazi, A., Battiti, F. O., Sanchez, J., Zaidi, S. A., Bow, E., Makarova, M., …Newman, A. H. (2021). Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management. Journal of Medicinal Chemistry, 64(11), 7778-7808. https://doi.org/10.1021/acs.jmedchem.1c00611

The need for safer pain-management therapies with decreased abuse liability inspired a novel drug design that retains μ-opioid receptor (MOR)-mediated analgesia, while minimizing addictive liability. We recently demonstrated that targeting the dopami... Read More about Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management.

Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14 (2021)
Journal Article
Wang, S., Foster, S. R., Sanchez, J., Corcilius, L., Larance, M., Canals, M., …Payne, R. J. (2021). Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14. ACS Chemical Biology, 16(6), 973-981. https://doi.org/10.1021/acschembio.1c00006

Chemokines are secreted proteins that regulate leukocyte migration during inflammatory responses by signaling through chemokine receptors. Full length CC chemokine ligand 14, CCL14(1–74), is a weak agonist for the chemokine receptor CCR1, but its act... Read More about Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14.

Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10 (2021)
Journal Article
Lim, H. D., Robert Lane, J., Canals, M., & Stone, M. J. (2021). Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10. International Journal of Molecular Sciences, 22(8), Article 4232. https://doi.org/10.3390/ijms22084232

Chemokines interact with chemokine receptors in a promiscuous network, such that each receptor can be activated by multiple chemokines. Moreover, different chemokines have been reported to preferentially activate different signalling pathways via the... Read More about Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10.

New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling (2021)
Journal Article
Mann, A., Keen, A. C., Mark, H., Dasgupta, P., Javitch, J. A., Canals, M., …Robert Lane, J. (2022). New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling. Scientific Reports, 11(1), Article 8288. https://doi.org/10.1038/s41598-021-87417-2

The dopamine D2 receptor (D2R) is the target of drugs used to treat the symptoms of Parkinson’s disease and schizophrenia. The D2R is regulated through its interaction with and phosphorylation by G protein receptor kinases (GRKs) and interaction with... Read More about New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling.

A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes (2021)
Journal Article
Mai, Q. N., Shenoy, P., Quach, T., Retamal, J. S., Gondin, A. B., Yeatman, H. R., …Veldhuis, N. A. (2021). A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes. Journal of Biological Chemistry, 296, Article 100345. https://doi.org/10.1016/J.JBC.2021.100345

G-protein-coupled receptors (GPCRs) are traditionally known for signaling at the plasma membrane, but they can also signal from endosomes after internalization to control important pathophysiological processes. In spinal neurons, sustained endosomal... Read More about A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes.