Constitutive Activity and Inverse Agonists of G Protein-Coupled Receptors: a Current Perspective: TABLE 1

2003 ◽  
Vol 64 (6) ◽  
pp. 1271-1276 ◽  
Author(s):  
Graeme Milligan
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Constitutive Activity ◽  
Inverse Agonists ◽  
Current Perspective ◽  
G Protein Coupled ◽  
A Current

scholarly journals Constitutive Activity among Orphan Class-A G Protein Coupled Receptors

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0138463 ◽  
Author(s):  
Adam L. Martin ◽  
Michael A. Steurer ◽  
Robert S. Aronstam
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Constitutive Activity ◽  
Class A ◽  
G Protein Coupled

scholarly journals BRET Analysis of GPCR Dimers in Neurons and Non-Neuronal Cells: Evidence for Inactive, Agonist, and Constitutive Conformations

2021 ◽  
Vol 22 (19) ◽  
pp. 10638
Author(s):  
Chayma El Khamlichi ◽  
Laetitia Cobret ◽  
Jean-Michel Arrang ◽  
Séverine Morisset-Lopez
Keyword(s):  
Cortical Neurons ◽  
G Protein Coupled Receptors ◽  
Constitutive Activity ◽  
Western Blots ◽  
Inverse Agonists ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Functional Consequences ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) are dimeric proteins, but the functional consequences of the process are still debated. Active GPCR conformations are promoted either by agonists or constitutive activity. Inverse agonists decrease constitutive activity by promoting inactive conformations. The histamine H3 receptor (H3R) is the target of choice for the study of GPCRs because it displays high constitutive activity. Here, we study the dimerization of recombinant and brain H3R and explore the effects of H3R ligands of different intrinsic efficacy on dimerization. Co-immunoprecipitations and Western blots showed that H3R dimers co-exist with monomers in transfected HEK 293 cells and in rodent brains. Bioluminescence energy transfer (BRET) analysis confirmed the existence of spontaneous H3R dimers, not only in living HEK 293 cells but also in transfected cortical neurons. In both cells, agonists and constitutive activity of the H3R decreased BRET signals, whereas inverse agonists and GTPγS, which promote inactive conformations, increased BRET signals. These findings show the existence of spontaneous H3R dimers not only in heterologous systems but also in native tissues, which are able to adopt a number of allosteric conformations, from more inactive to more active states.

G protein-coupled receptors serve as mechanosensors for fluid shear stress in neutrophils

2006 ◽  
Vol 290 (6) ◽  
pp. C1633-C1639 ◽  
Author(s):  
Ayako Makino ◽  
Eric R. Prossnitz ◽  
Moritz Bünemann ◽  
Ji Ming Wang ◽  
Weijuan Yao ◽  
...  
Keyword(s):  
Shear Stress ◽  
G Protein ◽  
Fluid Shear Stress ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Specific Response ◽  
Constitutive Activity ◽  
Fluid Shear ◽  
Hl60 Cells ◽  
G Protein Coupled

Many cells respond to fluid shear stress but in a cell type-specific fashion. Fluid shear stress applied to leukocytes serves to control pseudopod formation, migration, and other functions. Specifically, fresh neutrophils or neutrophilic leukocytes derived from differentiated HL60 cells respond to fluid shear stress by cytoplasmic pseudopod retraction. The membrane elements that sense fluid shear and induce such a specific response are still unknown, however. We hypothesized that membrane receptors may serve as fluid shear sensors. We found that fluid shear decreased the constitutive activity of G protein-coupled receptors (GPCRs). Inhibition of GPCR constitutive activity by inverse agonists abolished fluid shear stress-induced cell area reduction. Among the GPCRs in neutrophils, the formyl peptide receptor (FPR) exhibits relatively high constitutive activity. Undifferentiated HL60 cells that lacked FPR formed few pseudopods and showed no detectable response to fluid shear stress, whereas expression of FPR in undifferentiated HL60 cells caused pseudopod projection and robust pseudopod retraction during fluid shear. FPR small interfering RNA-transfected differentiated HL60 cells exhibited no response to fluid shear stress. These results suggest that GPCRs serve as mechanosensors for fluid shear stress in neutrophils by decreasing its constitutive activity and reducing pseudopod projection.

Constitutive activity of G protein coupled receptors and drug action

2000 ◽  
Vol 74 (2-3) ◽  
pp. 327-331 ◽  
Author(s):  
Rob Leurs ◽  
Maria Sol Rodriguez Pena ◽  
Remko A Bakker ◽  
Astrid E Alewijnse ◽  
Henk Timmerman
Keyword(s):  
G Protein ◽  
Drug Action ◽  
G Protein Coupled Receptors ◽  
Constitutive Activity ◽  
G Protein Coupled

scholarly journals Differences in the pharmacological activation of visual opsins

2006 ◽  
Vol 23 (6) ◽  
pp. 899-908 ◽  
Author(s):  
T. ISAYAMA ◽  
Y. CHEN ◽  
M. KONO ◽  
W.J. DEGRIP ◽  
J.-X. MA ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Constitutive Activity ◽  
Rods And Cones ◽  
Cone Opsin ◽  
Specific Effects ◽  
Structural Differences ◽  
Cone Opsins ◽  
G Protein Coupled ◽  
Flash Response

Opsins, like many other G-protein-coupled receptors, sustain constitutive activity in the absence of ligand. In partially bleached rods and cones, opsin's activity closes cGMP-gated channels and produces a state of “pigment adaptation” with reduced sensitivity to light and accelerated flash response kinetics. The truncated retinal analogue, β-ionone, further desensitizes partially bleached green-sensitive salamander rods, but enables partially bleached red-sensitive cones to recover dark-adapted physiology. Structural differences between rod and cone opsins were proposed to explain the effect. Rods and cones, however, also contain different transducins, raising the possibility that G-protein type determines the photoreceptor-specific effects of β-ionone. To test the two hypotheses, we applied β-ionone to partially bleached blue-sensitive rods and cones of salamander, two cells that couple the same cone-like opsin to either rod or cone transducin, respectively. Immunocytochemistry confirmed that all salamander rods contain one form of transducin, whereas all cones contain another. β-Ionone enhanced pigment adaptation in blue-sensitive rods, but it also did so in blue- and UV-sensitive cones. Furthermore, all recombinant salamander rod and cone opsins, with the exception of the red-sensitive cone opsin, activated rod transducin upon the addition of β-ionone. Thus opsin structure determines the identity of β-ionone as an agonist or an inverse agonist and in that respect distinguishes the red-sensitive cone opsin from all others.

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