scholarly journals Cannabinoid Receptor Type 1 (CB1) Activation Inhibits Small GTPase RhoA Activity and Regulates Motility of Prostate Carcinoma Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 29-41 ◽  
Author(s):  
Kasem Nithipatikom ◽  
Ana Doris Gomez-Granados ◽  
Alan T. Tang ◽  
Adam W. Pfeiffer ◽  
Carol L. Williams ◽  
...  
Keyword(s):  
Cell Migration ◽  
Prostate Carcinoma ◽  
Cannabinoid Receptor ◽  
Cell Spreading ◽  
Small Gtpase ◽  
Carcinoma Cells ◽  
Receptor Type ◽  
Rhoa Activity ◽  
Cannabinoid Receptor Type 1

The cannabinoid receptor type 1 (CB1) is a G protein-coupled receptor that is activated in an autocrine fashion by the endocannabinoids (EC), N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). The CB1 and its endogenous and synthetic agonists are emerging as therapeutic targets in several cancers due to their ability to suppress carcinoma cell invasion and migration. However, the mechanisms that the CB1 regulates cell motility are not well understood. In this study, we examined the molecular mechanisms that diminish cell migration upon the CB1 activation in prostate carcinoma cells. The CB1 activation with the agonist WIN55212 significantly diminishes the small GTPase RhoA activity but modestly increases the Rac1 and Cdc42 activity. The diminished RhoA activity is accompanied by the loss of actin/myosin microfilaments, cell spreading, and cell migration. Interestingly, the CB1 inactivation with the selective CB1 antagonist AM251 significantly increases RhoA activity, enhances microfilament formation and cell spreading, and promotes cell migration. This finding suggests that endogenously produced EC activate the CB1, resulting in chronic repression of RhoA activity and cell migration. Consistent with this possibility, RhoA activity is significantly diminished by the exogenous application of AEA but not by 2-AG in PC-3 cells (cells with very low AEA hydrolysis). Pretreatment of cells with a monoacylglycerol lipase inhibitor, JZL184, which blocks 2-AG hydrolysis, decreases the RhoA activity. These results indicate the unique CB1 signaling and support the model that EC, through their autocrine activation of CB1 and subsequent repression of RhoA activity, suppress migration in prostate carcinoma cells.

Cannabinoid Receptor Type 1 and mu-Opioid Receptor Polymorphisms Are Associated With Cyclic Vomiting Syndrome

2017 ◽  
Vol 112 (6) ◽  
pp. 933-939 ◽  
Author(s):  
Andrzej Wasilewski ◽  
Urszula Lewandowska ◽  
Paula Mosinska ◽  
Cezary Watala ◽  
Martin Storr ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Cannabinoid Receptor ◽  
Mu Opioid Receptor ◽  
Receptor Type ◽  
Cyclic Vomiting Syndrome ◽  
Mu Opioid ◽  
Cannabinoid Receptor Type 1 ◽  
Cyclic Vomiting

Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling

2020 ◽  
Vol 34 (4) ◽  
pp. 429-440
Author(s):  
Lucas Gomes-de-Souza ◽  
Willian Costa-Ferreira ◽  
Leandro A Oliveira ◽  
Ricardo Benini ◽  
Carlos C Crestani
Keyword(s):  
Nitric Oxide ◽  
Receptor Antagonist ◽  
Restraint Stress ◽  
Cannabinoid Receptor ◽  
Cardiovascular Responses ◽  
Receptor Type ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Cannabinoid Receptor Type 1

Background: Endocannabinoid neurotransmission in the bed nucleus of the stria terminalis is involved in the control of cardiovascular responses to stress. However, the local mechanisms involved is this regulation are not known. Aims: The purpose of this study was to assess an interaction of bed nucleus of the stria terminalis endocannabinoid neurotransmission with local nitrergic signaling, as well as to investigate the involvement of local N-methyl-D-aspartate glutamate receptor and nitric oxide signaling in the control of cardiovascular responses to acute restraint stress by bed nucleus of the stria terminalis endocannabinoid neurotransmission in rats. Methods: The first protocol evaluated the effect of intra-bed nucleus of the stria terminalis microinjection of the selective cannabinoid receptor type 1 receptor antagonist AM251 in nitrite/nitrate content in the bed nucleus of the stria terminalis following restraint stress. The other protocols evaluated the impact of local pretreatment with the selective N-methyl-D-aspartate glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase inhibitor Nω-propyl-L-arginine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the protein kinase G inhibitor KT5823 in restraint-evoked cardiovascular changes following bed nucleus of the stria terminalis treatment with AM251. Results: Bilateral microinjection of AM251 into the bed nucleus of the stria terminalis increased local nitric oxide release during restraint stress. Bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist also enhanced the tachycardia caused by restraint stress, but without affecting arterial pressure increase and sympathetic-mediated cutaneous vasoconstriction. The facilitation of restraint-evoked tachycardia following bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist was completely inhibited by local pretreatment with LY235959, Nω-propyl-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or KT5823. Conclusions: Our results provide evidence that bed nucleus of the stria terminalis endocannabinoid neurotransmission inhibits local N-methyl-D-aspartate/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling, and this mechanism is involved in the control of the cardiovascular responses to stress.

Cannabinoid receptor Type 1 densities reflect social organization in Microtus

2020 ◽  
Author(s):  
Trenton C. Simmons ◽  
Sara M. Freeman ◽  
Nicholas S. Lackey ◽  
Brooke K. Dreyer ◽  
Devanand S. Manoli ◽  
...  
Keyword(s):  
Social Organization ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 1

Inverse agonist of ERRγ reduces cannabinoid receptor type 1-mediated induction of fibrinogen synthesis in mice with a high-fat diet-intoxicated liver

2018 ◽  
Vol 92 (9) ◽  
pp. 2885-2896 ◽  
Author(s):  
Yaochen Zhang ◽  
Don-Kyu Kim ◽  
Yoon Seok Jung ◽  
Yong-Hoon Kim ◽  
Yong Soo Lee ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Cannabinoid Receptor ◽  
Inverse Agonist ◽  
Receptor Type ◽  
High Fat ◽  
Cannabinoid Receptor Type 1

scholarly journals Test–retest reproducibility of cannabinoid-receptor type 1 availability quantified with the PET ligand [11C]MePPEP

NeuroImage ◽  
2014 ◽  
Vol 97 ◽  
pp. 151-162 ◽  
Author(s):  
Daniela A. Riaño Barros ◽  
Colm J. McGinnity ◽  
Lula Rosso ◽  
Rolf A. Heckemann ◽  
Oliver D. Howes ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 1
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