Ion Channel Regulation by G-Protein-Coupled Receptors: Recent Advances with Optical Biosensors

2013 ◽  
pp. 1129-1135
Author(s):  
Mark S. Shapiro
Keyword(s):  
Ion Channel ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Optical Biosensors ◽  
Ion Channel Regulation ◽  
Channel Regulation ◽  
Recent Advances ◽  
G Protein Coupled

scholarly journals Nociceptor Signalling through ion Channel Regulation via GPCRs

2019 ◽  
Vol 20 (10) ◽  
pp. 2488 ◽  
Author(s):  
Isabella Salzer ◽  
Sutirtha Ray ◽  
Klaus Schicker ◽  
Stefan Boehm
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Ion Channel Regulation ◽  
Nociceptive Neurons ◽  
Channel Modulation ◽  
Ion Channel Modulation ◽  
Endogenous Modulators ◽  
G Protein Coupled

The prime task of nociceptors is the transformation of noxious stimuli into action potentials that are propagated along the neurites of nociceptive neurons from the periphery to the spinal cord. This function of nociceptors relies on the coordinated operation of a variety of ion channels. In this review, we summarize how members of nine different families of ion channels expressed in sensory neurons contribute to nociception. Furthermore, data on 35 different types of G protein coupled receptors are presented, activation of which controls the gating of the aforementioned ion channels. These receptors are not only targeted by more than 20 separate endogenous modulators, but can also be affected by pharmacotherapeutic agents. Thereby, this review provides information on how ion channel modulation via G protein coupled receptors in nociceptors can be exploited to provide improved analgesic therapy.

Recent Advances of Small Molecular Regulators Targeting G Protein- Coupled Receptors Family for Oncology Immunotherapy

2019 ◽  
Vol 19 (16) ◽  
pp. 1464-1483 ◽  
Author(s):  
Peng He ◽  
Wenbo Zhou ◽  
Mingyao Liu ◽  
Yihua Chen
Keyword(s):  
G Protein ◽  
Cell Biology ◽  
Immune Cell ◽  
G Protein Coupled Receptors ◽  
Treatment Modalities ◽  
Immune Checkpoints ◽  
Considerable Proportion ◽  
Prostaglandin E ◽  
Recent Advances ◽  
G Protein Coupled

The great clinical success of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggests the drawing of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G Protein-Coupled Receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, prostaglandin E receptor EP4 and opioid receptors. Moreover, we outline how they affect tumor immunity and neoplasia by regulating immune cell recruitment and modulating tumor stromal cell biology. We also summarize the data from recent clinical advances in small molecular regulators targeting these GPCRs, in combination with immune checkpoints blockers, such as PD-1/PDL-1 and CTLA4 inhibitors, for cancer treatments.

Ion channel regulation by G proteins

1995 ◽  
Vol 75 (4) ◽  
pp. 865-885 ◽  
Author(s):  
K. Wickman ◽  
D. E. Clapham
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
G Protein ◽  
G Proteins ◽  
Second Messengers ◽  
Channel Activity ◽  
Ion Channel Regulation ◽  
Protein Subunits ◽  
Channel Regulation ◽  
Intracellular Cascades

Ion channels are poised uniquely to initiate, mediate, or regulate such distinct cellular activities as action potential propagation, secretion, and gene transcription. In retrospect, it is not surprising that studies of ion channels have revealed considerable diversities in their primary structures, regulation, and expression. From a functional standpoint, the various mechanisms coopted by cells to regulate channel activity are particularly fascinating. Extracellular ligands, membrane potential, phosphorylation, ions themselves, and diffusible second messengers are all well-established regulators of ion channel activity. Heterotrimeric GTP-binding proteins (G proteins) mediate many of these types of ion channel regulation by stimulating or inhibiting phosphorylation pathways, initiating intracellular cascades leading to elevation of cytosolic Ca2+ or adenosine 3',5'-cyclic monophosphate levels, or by generating various lipid-derived compounds. In some cases, it seems that activated G protein subunits can interact directly with ion channels to elicit regulation. Although there is currently little direct biochemical evidence to support such a mechanism, it is the working hypothesis for the most-studied G protein-regulated ion channels.

Recent Advances in the Drug Discovery and Development of Dualsteric/ Bitopic Activators of G Protein-Coupled Receptors

2019 ◽  
Vol 19 (26) ◽  
pp. 2378-2392 ◽  
Author(s):  
Bethany A. Reinecke ◽  
Huiqun Wang ◽  
Yan Zhang
Keyword(s):  
G Protein ◽  
Binding Affinity ◽  
G Protein Coupled Receptors ◽  
Allosteric Modulator ◽  
High Binding ◽  
Subtype Selectivity ◽  
Recent Advances ◽  
Allosteric Sites ◽  
G Protein Coupled ◽  
High Binding Affinity

G protein-coupled receptors (GPCRs) represent the largest family of proteins targeted by drug design and discovery efforts. Of these efforts, the development of GPCR agonists is highly desirable, due to their therapeutic robust utility in treating diseases caused by deficient receptor signaling. One of the challenges in designing potent and selective GPCR agonists lies in the inability to achieve combined high binding affinity and subtype selectivity, due to the high homology between orthosteric sites among GPCR subtypes. To combat this difficulty, researchers have begun to explore the utility of targeting topographically distinct and less conserved binding sites, namely “allosteric” sites. Pursuing these sites offers the benefit of achieving high subtype selectivity, however, it also can result in a decreased binding affinity and potency as compared to orthosteric agonists. Therefore, bitopic ligands comprised of an orthosteric agonist and an allosteric modulator connected by a spacer and allowing binding with both the orthosteric and allosteric sites within one receptor, have been developed. It may combine the high subtype selectivity of an allosteric modulator with the high binding affinity of an orthosteric agonist and provides desired advantages over orthosteric agonists or allosteric modulators alone. Herein, we review the recent advances in the development of bitopic agonists/activators for various GPCR targets and their novel therapeutic potentials.

scholarly journals Functional Assay for T4 Lysozyme-Engineered G Protein-Coupled Receptors with an Ion Channel Reporter

Structure ◽  
2014 ◽  
Vol 22 (1) ◽  
pp. 149-155 ◽  
Author(s):  
Katarzyna Niescierowicz ◽  
Lydia Caro ◽  
Vadim Cherezov ◽  
Michel Vivaudou ◽  
Christophe J. Moreau
Keyword(s):  
Ion Channel ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Functional Assay ◽  
T4 Lysozyme ◽  
G Protein Coupled

scholarly journals Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

2016 ◽  
Vol 18 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Rosamaria Lappano ◽  
Damiano Rigiracciolo ◽  
Paola De Marco ◽  
Silvia Avino ◽  
Anna Rita Cappello ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Recent Advances ◽  
G Protein Coupled

scholarly journals Recent advances in multitarget-directed ligands targeting G-protein-coupled receptors

2020 ◽  
Vol 25 (9) ◽  
pp. 1682-1692
Author(s):  
Hongguang Ma ◽  
Boshi Huang ◽  
Yan Zhang
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Recent Advances ◽  
G Protein Coupled
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