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Novel Mechanisms of Receptor Activation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 2213

Special Issue Editor


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Guest Editor
College of Life Sciences, Beijing Normal University, Beijing 100875, China
Interests: cholecystokinin receptors; G protein-coupled receptors; singlet oxgen; photodynamic biology; ligand-independent receptor activation; receptor pharmacology; receptor monomerizarion; calcium oscillations
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Special Issue Information

Dear Colleagues,

Different types of cells respond to specific external signals via the cell surface and intracellular receptors. Conventional receptor pharmacology includes the binding of both orthosteric and allosteric ligands. Examples of ligand-independent receptor activation and modulations are also abundant and increasingly common; ligand-independent receptor activation is probably equally important. Furthermore, ligand-independent receptor activation could solve important problems not readily addressed by conventional receptor pharmacology. In fact, some spontaneous cellular activities and physiological processes/functions could actually occur due to the non-typical activation of receptors independent of binding by any ligands. In this Special Issue, we wish to bring together work from all areas of receptor activation and receptor pharmacology, identifying unconventional and novel modes and mechanisms of receptor activation and signalling. Target receptors could be G protein-coupled receptors (GPCRs), or receptors of any other types—both on the surface and in the interiors of cells. Submissions may be from the following and related areas:

  1. Agonist-stimulated activation of GPCRs;
  2. Ligand-independent activation of GPCRs;
  3. Constitutive activation of (viral) GPCRs;
  4. Photodynamic (light-driven) receptor activation;
  5. Voltage-driven receptor activation/modulation;
  6. Oxidative activation of receptors;
  7. Receptor activation via phosphorylation or other posttranslational modifications;
  8. Mechanosensitive GPCRs;
  9. Receptor monomerization/dimerization/oligomerization/clustering;
  10. Pharmacophores/structural motifs important for receptor activation.

Prof. Dr. Zong Jie Cui
Guest Editor

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Keywords

  • G protein-coupled receptors
  • nuclear (steroid) hormone receptors
  • catalytic receptors
  • receptor structural motifs important for activation
  • receptor pharmacophores
  • structure–function correlates
  • cellular functions
  • integrated physiology
  • compartmentalized GPCRs
  • receptor pharmacology
  • aryl hydrocarbon receptor (AHR)
  • “orphan” GPCRs

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Published Papers (2 papers)

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Research

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22 pages, 4291 KB  
Article
Photodynamic Activation of Mammalian and Avian Cholecystokinin Type 1 Receptor Outside of the Pancreatic Acinar Cell Microenvironment
by Jie Wang and Zong Jie Cui
Int. J. Mol. Sci. 2025, 26(24), 12011; https://doi.org/10.3390/ijms262412011 - 13 Dec 2025
Viewed by 662
Abstract
Cholecystokinin 1 receptor (CCK1R) is activated by singlet oxygen (1O2) in type II photodynamic action in isolated rat, mouse, and Peking duck pancreatic acini. To examine whether this is maintained outside the microenvironment of pancreatic acinar cell, photodynamic activation [...] Read more.
Cholecystokinin 1 receptor (CCK1R) is activated by singlet oxygen (1O2) in type II photodynamic action in isolated rat, mouse, and Peking duck pancreatic acini. To examine whether this is maintained outside the microenvironment of pancreatic acinar cell, photodynamic activation of CCK1R from human, rat, mouse, and Peking duck expressed in CHO-K1 cells was examined, as monitored with Fura-2 fluorescence calcium imaging. Photodynamic action with sulphonated aluminum phthalocyanine was found to trigger persistent calcium oscillations in CCK1R-CHO-K1 cells transfected with human, rat, mouse or Peking duck CCK1R gene, which were blocked by 1O2 quencher Trolox C. After tagging protein photosensitizer miniSOG to C-terminus of these CCK1R, photodynamic action was found to similarly trigger persistent calcium oscillations in CCK1R-miniSOG-CHO-K1 cells expressing human, rat, mouse, and Peking duck receptor constructs. Incubation with Trolox C 300 μM during LED light irradiation also prevented photodynamic CCK1R activation in CCK1R-miniSOG-CHO-K1 cells. In contrast, human M3R was not photodynamically activated with SALPC or tagged miniSOG as the photosensitizer. These data, together, suggest that photodynamic CCK1R activation is maintained outside of the pancreatic acinar cell, making possible photodynamic CCK1R activation in CCK1R-expressing organs and tissues other than the pancreas, with high spatiotemporal precision. Full article
(This article belongs to the Special Issue Novel Mechanisms of Receptor Activation)
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Review

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21 pages, 1387 KB  
Review
Modulation of Nociceptive Ion Channels by Protease-Activated Receptor-2 in Inflammatory Pain: Molecular Mechanisms and Therapeutic Potential
by Haneen Aburamadan, Yosra Lozon, Asha Caroline Cyril, Anagha Nelliyulla Parambath, Najma Mohamed Ali, Reem Kais Jan, Robin Plevin and Rajan Radhakrishnan
Int. J. Mol. Sci. 2026, 27(4), 1769; https://doi.org/10.3390/ijms27041769 - 12 Feb 2026
Viewed by 1004
Abstract
Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor (GPCR) expressed in both the peripheral and central nervous systems. It plays a pivotal role in mediating neuroimmune interactions, particularly in the context of inflammation and pain. Upon activation by proteases, PAR2 modulates nociception [...] Read more.
Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor (GPCR) expressed in both the peripheral and central nervous systems. It plays a pivotal role in mediating neuroimmune interactions, particularly in the context of inflammation and pain. Upon activation by proteases, PAR2 modulates nociception through signaling cascades that influence key ion channels, including transient receptor potential (TRP) ion channels vanilloid 1 and 4 (TRPV1 and TRPV4), ankyrin 1 (TRPA1), acid-sensing ion channel 3 (ASIC3), P2X purinoceptor 3 (P2X3), Cav3.2 (T-type Ca2+ channel), and potassium Kv7 (M-current) channels, altering their expression and function. Through this crosstalk, PAR2 contributes to heightened neuronal excitability and pain hypersensitivity in various inflammatory conditions. In this narrative review, we highlight and discuss the mechanistic and functional interplay between PAR2 and nociceptive ion channels, which might be contributing to the pathogenesis of inflammatory pain. Targeting these specific molecular interactions between PAR2 and nociceptive ion channels may offer a promising therapeutic strategy for treating inflammatory pain. Full article
(This article belongs to the Special Issue Novel Mechanisms of Receptor Activation)
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