Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon

2015 ◽  
Vol 758 ◽  
pp. 153-163 ◽  
Author(s):  
Juliana Almeida da Silva ◽  
Audrey Francisco Biagioni ◽  
Rafael Carvalho Almada ◽  
José Alexandre de Souza Crippa ◽  
Jaime Eduardo Cecílio Hallak ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Cannabinoid Receptor ◽  
Substantia Nigra Pars Reticulata ◽  
Ventral Mesencephalon ◽  
Cb1 Cannabinoid Receptor ◽  
Deep Layers

scholarly journals Mutations in the ‘DRY’ motif of the CB1 cannabinoid receptor result in biased receptor variants

2014 ◽  
Vol 54 (1) ◽  
pp. 75-89 ◽  
Author(s):  
Pál Gyombolai ◽  
András D Tóth ◽  
Dániel Tímár ◽  
Gábor Turu ◽  
László Hunyady
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Double Mutant ◽  
Cannabinoid Receptor ◽  
Camp Accumulation ◽  
Protein Activation ◽  
Cb1 Cannabinoid Receptor ◽  
G Protein Activation ◽  
Dry Motif

The role of the highly conserved ‘DRY’ motif in the signaling of the CB1cannabinoid receptor (CB1R) was investigated by inducing single-, double-, and triple-alanine mutations into this site of the receptor. We found that the CB1R-R3.50A mutant displays a partial decrease in its ability to activate heterotrimeric Goproteins (∼80% of WT CB1R (CB1R-WT)). Moreover, this mutant showed an enhanced basal β-arrestin2 (β-arr2) recruitment. More strikingly, the double-mutant CB1R-D3.49A/R3.50A was biased toward β-arrs, as it gained a robustly increased β-arr1 and β-arr2 recruitment ability compared with the WT receptor, while its G-protein activation was decreased. In contrast, the double-mutant CB1R-R3.50A/Y3.51A proved to be G-protein-biased, as it was practically unable to recruit β-arrs in response to agonist stimulus, while still activating G-proteins, although at a reduced level (∼70% of CB1R-WT). Agonist-induced ERK1/2 activation of the CB1R mutants showed a good correlation with their β-arr recruitment ability but not with their G-protein activation or inhibition of cAMP accumulation. Our results suggest that G-protein activation and β-arr binding of the CB1R are mediated by distinct receptor conformations, and the conserved ‘DRY’ motif plays different roles in the stabilization of these conformations, thus mediating both G-protein- and β-arr-mediated functions of CB1R.

scholarly journals Superior Colliculus Mediates Cervical Dystonia Evoked by Inhibition of the Substantia Nigra Pars Reticulata

2012 ◽  
Vol 32 (38) ◽  
pp. 13326-13332 ◽  
Author(s):  
A. L. Holmes ◽  
P. A. Forcelli ◽  
J. T. DesJardin ◽  
A. L. Decker ◽  
M. Teferra ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Cervical Dystonia ◽  
Substantia Nigra Pars Reticulata
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