scholarly journals In vivo Evidence for Brain Region-Specific Molecular Interactions Between Cannabinoid and Orexin Receptors

2021 ◽  
Vol 15 ◽  
Author(s):  
Hye Ji J. Kim ◽  
Ayat Zagzoog ◽  
Anna Maria Smolyakova ◽  
Udoka C. Ezeaka ◽  
Michael J. Benko ◽  
...  
Keyword(s):  
Body Temperature ◽  
Molecular Interactions ◽  
Brain Region ◽  
Ventral Striatum ◽  
Cannabinoid Receptor ◽  
Combined Treatment ◽  
Neuronal Cell ◽  
Receptor Type ◽  
Valuable Insight

The endocannabinoid and orexin neuromodulatory systems serve key roles in many of the same biological functions such as sleep, appetite, pain processing, and emotional behaviors related to reward. The type 1 cannabinoid receptor (CB1R) and both subtypes of the orexin receptor, orexin receptor type 1 (OX1R) and orexin receptor type 2 (OX2R) are not only expressed in the same brain regions modulating these functions, but physically interact as heterodimers in recombinant and neuronal cell cultures. In the current study, male and female C57BL/6 mice were co-treated with the cannabinoid receptor agonist CP55,940 and either the OX2R antagonist TCS-OX2-29 or the dual orexin receptor antagonist (DORA) TCS-1102. Mice were then evaluated for catalepsy, body temperature, thermal anti-nociception, and locomotion, after which their brains were collected for receptor colocalization analysis. Combined treatment with the DORA TCS-1102 and CP55,940 potentiated catalepsy more than CP55,940 alone, but this effect was not observed for changes in body temperature, nociception, locomotion, or via selective OX2R antagonism. Co-treatment with CP55,940 and TCS-1102 also led to increased CB1R-OX1R colocalization in the ventral striatum. This was not seen following co-treatment with TCS-OX2-29, nor in CB1R-OX2R colocalization. The magnitude of effects following co-treatment with CP55,940 and either the DORA or OX2R-selective antagonist was greater in males than females. These data show that CB1R-OX1R colocalization in the ventral striatum underlies cataleptic additivity between CP55,940 and the DORA TCS-1102. Moreover, cannabinoid-orexin receptor interactions are sex-specific with regards to brain region and functionality. Physical or molecular interactions between these two systems may provide valuable insight into drug-drug interactions between cannabinoid and orexin drugs for the treatment of insomnia, pain, and other disorders.

Mitochondrial Localization of CB1 in Progesterone-producing Cells of Ovarian Interstitial Glands of Adult Mice

2021 ◽  
pp. 002215542110635
Author(s):  
Anussara Kamnate ◽  
Juthathip Sirisin ◽  
Masahiko Watanabe ◽  
Hisatake Kondo ◽  
Wiphawi Hipkaeo ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Mitochondrial Localization ◽  
Mitochondrial Membranes ◽  
Synthetic Process ◽  
Outer Membranes ◽  
Adult Mice

Localization of cannabinoid receptor type 1 (CB1) immunoreactivity on mitochondrial membranes, at least their outer membranes distinctly, was detected in progesterone-producing cells characterized by mitochondria having tubular cristae and aggregations of lipid droplets in ovarian interstitial glands in situ of adult mice. Both immunoreactive and immunonegative mitochondria were contained in one and the same cell. Considering that the synthesis of progesterone is processed in mitochondria, the mitochondrial localization of CB1 in the interstitial gland cells suggests the possibility that endocannabinoids modulate the synthetic process of progesterone in the cells through CB1:

scholarly journals Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Andrea Mastinu ◽  
Marika Premoli ◽  
Giulia Ferrari-Toninelli ◽  
Simone Tambaro ◽  
Giuseppina Maccarinelli ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
History Of ◽  
Health And Disease ◽  
Pharmacological Potential ◽  
The Brain ◽  
Synthesis And Degradation

Abstract The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response. In this review a brief history of cannabinoids and the protagonists of the endocannabinoidergic system, i.e. synthesis and degradation enzymes and main receptors, will be described. Furthermore, the pharmacological effects of cannabinoids will be outlined. An overview of the involvement of the endocannabinoidergic system in neuroinflammatory and metabolic pathologies will be made. Finally, particular attention will also be given to the new pharmacological entities acting on the two main receptors, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), with particular focus on the neuroinflammatory and metabolic mechanisms involved.

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

scholarly journals Orphan nuclear receptor oestrogen-related receptor γ (ERRγ) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression

2015 ◽  
Vol 470 (2) ◽  
pp. 181-193 ◽  
Author(s):  
Yaochen Zhang ◽  
Don-Kyu Kim ◽  
Ji-Min Lee ◽  
Seung Bum Park ◽  
Won-IL Jeong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Acid ◽  
Nuclear Receptor ◽  
Cannabinoid Receptor ◽  
Inverse Agonist ◽  
Receptor Type ◽  
Orphan Nuclear Receptor ◽  
Transcription Regulator ◽  
Estrogen Related Receptor

ERRγ is a novel transcription regulator of CYP7A1 (cholesterol 7α-hydroxylase). An ERRγ (Estrogen-related receptor γ) inverse agonist modulates bile acid homoeostasis via regulation of CYP7A1 gene expression.

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