Subchronic haloperidol increases CB1 receptor binding and G protein coupling in discrete regions of the basal ganglia

2005 ◽  
Vol 82 (2) ◽  
pp. 264-272 ◽  
Author(s):  
Mikael Andersson ◽  
Anton Terasmaa ◽  
Kjell Fuxe ◽  
Ingrid Strömberg
Keyword(s):  
Basal Ganglia ◽  
G Protein ◽  
Receptor Binding ◽  
Cb1 Receptor ◽  
G Protein Coupling ◽  
Protein Coupling

scholarly journals Increased opioid receptor binding and G protein coupling in the accumbens and ventral tegmental area of postnatal day 2 rats

2006 ◽  
Vol 395 (3) ◽  
pp. 244-248 ◽  
Author(s):  
Yanning Hou ◽  
Mariana M. Belcheva ◽  
Amy L. Clark ◽  
Daniel S. Zahm ◽  
Carmine J. Coscia
Keyword(s):  
Ventral Tegmental Area ◽  
G Protein ◽  
Opioid Receptor ◽  
Receptor Binding ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Ventral Tegmental ◽  
Opioid Receptor Binding

P.2.d.013 Cannabinoid CB1 receptor expression and G protein coupling in a genetic model of depression

2011 ◽  
Vol 21 ◽  
pp. S408-S409
Author(s):  
V.C. Sousa ◽  
X. Zhang ◽  
H. Qi ◽  
M. El Yacoubi ◽  
J.M. Vaugeois ◽  
...  
Keyword(s):  
G Protein ◽  
Genetic Model ◽  
Cb1 Receptor ◽  
Receptor Expression ◽  
Cannabinoid Cb1 Receptor ◽  
G Protein Coupling ◽  
Protein Coupling

scholarly journals Mechanistic insights into dopaminergic and serotonergic neurotransmission – concerted interactions with helices 5 and 6 drive the functional outcome

2021 ◽  
Author(s):  
Tomasz Maciej Stepniewski ◽  
Arturo Mancini ◽  
Richard Ågren ◽  
Mariona Torrens-Fontanals ◽  
Meriem Semache ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Binding Site ◽  
G Protein ◽  
Functional Response ◽  
Receptor Binding ◽  
Transmembrane Helix ◽  
Receptor Binding Site ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Serotonergic Neurotransmission

Neurotransmitter contacts within the receptor binding site differentially contribute to the overall functional response: transmembrane helix (TM) 5 contacts promote G protein coupling whereas concerted TM5–TM6 contacts enhance β-arrestin recruitment.

scholarly journals Allosteric Modulator ORG27569 Induces CB1 Cannabinoid Receptor High Affinity Agonist Binding State, Receptor Internalization, and Gi Protein-independent ERK1/2 Kinase Activation

2012 ◽  
Vol 287 (15) ◽  
pp. 12070-12082 ◽  
Author(s):  
Kwang H. Ahn ◽  
Mariam M. Mahmoud ◽  
Debra A. Kendall
Keyword(s):  
G Protein ◽  
Pertussis Toxin ◽  
Cannabinoid Receptor ◽  
Cb1 Receptor ◽  
Allosteric Modulator ◽  
Dependent Manner ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Agonist Affinity ◽  
The Impact

The cannabinoid receptor 1 (CB1), a member of the class A G protein-coupled receptor family, is expressed in brain tissue where agonist stimulation primarily activates the pertussis toxin-sensitive inhibitory G protein (Gi). Ligands such as CP55940 ((1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3- hydroxypropyl)cyclohexan-1-ol) and Δ9-tetrahydrocannabinol are orthosteric agonists for the receptor, bind the conventional binding pocket, and trigger Gi-mediated effects including inhibition of adenylate cyclase. ORG27569 (5-chloro-3-ethyl-1H-indole-2-carboxylic acid [2-(4-piperidin-1-yl-phenyl)ethyl]amide) has been identified as an allosteric modulator that displays positive cooperativity for CP55940 binding to CB1 yet acts as an antagonist of G protein coupling. To examine this apparent conundrum, we used the wild-type CB1 and two mutants, T210A and T210I (D'Antona, A. M., Ahn, K. H., and Kendall, D. A. (2006) Biochemistry 45, 5606–5617), which collectively cover a spectrum of receptor states from inactive to partially active to more fully constitutively active. Using these receptors, we demonstrated that ORG27569 induces a CB1 receptor state that is characterized by enhanced agonist affinity and decreased inverse agonist affinity consistent with an active conformation. Also consistent with this conformation, the impact of ORG27569 binding was most dramatic on the inactive T210A receptor and less pronounced on the already active T210I receptor. Although ORG27569 antagonized CP55940-induced guanosine 5′-3-O-(thio)triphosphate binding, which is indicative of G protein coupling inhibition in a concentration-dependent manner, the ORG27569-induced conformational change of the CB1 receptor led to cellular internalization and downstream activation of ERK signaling, providing the first case of allosteric ligand-biased signaling via CB1. ORG27569-induced ERK phosphorylation persisted even after pertussis toxin treatment to abrogate Gi and occurs in HEK293 and neuronal cells.

Defect of receptor-G protein coupling in human gallbladder with cholesterol stones

2000 ◽  
Vol 278 (2) ◽  
pp. G251-G258 ◽  
Author(s):  
Zuo-Liang Xiao ◽  
Qian Chen ◽  
Joseph Amaral ◽  
Piero Biancani ◽  
Jose Behar
Keyword(s):  
G Protein ◽  
Receptor Binding ◽  
Binding Capacity ◽  
G Protein Coupling ◽  
Human Gallbladder ◽  
Protein Coupling ◽  
Cck Receptors ◽  
Protein Quantitation ◽  
Gtpγs Binding ◽  
Contraction And Relaxation

Human gallbladders with cholesterol stones (ChS) exhibit an impaired muscle contraction and relaxation and a lower CCK receptor-binding capacity compared with those with pigment stones (PS). This study was designed to determine whether there is an abnormal receptor-G protein coupling in human gallbladders with ChS using35S-labeled guanosine 5′- O-(3-thiotriphosphate) ([35S]GTPγS) binding,125I-labeled CCK-8 autoradiography, immunoblotting, and G protein quantitation. CCK and vasoactive intestinal peptide caused significant increases in [35S]GTPγS binding to Gαi-3 and Gsα, respectively. The binding was lower in ChS than in PS ( P < 0.01). The reduced [35S]GTPγS binding in ChS was normalized after the muscles were treated with cholesterol-free liposomes ( P < 0.01). Autoradiography and immunoblots showed a decreased optical density (OD) for CCK receptors, an even lower OD value for receptor-G protein coupling, and a higher OD for uncoupled receptors or Gαi-3 protein in ChS compared with PS ( P < 0.001). G protein quantitation also showed that there were no significant differences in the Gαi-3 and Gsα content in ChS and PS. We conclude that, in addition to an impaired CCK receptor-binding capacity, there is a defect in receptor-G protein coupling in muscle cells from gallbladder with ChS. These changes may be normalized after removal of excess cholesterol from the plasma membrane.

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