Differential Treatment Regimen-Related Effects of HU210 on CB&lt;sub&gt;1&lt;/sub&gt; and D&lt;sub&gt;2&lt;/sub&gt;-Like Receptor Functionality in the Rat Basal Ganglia

Nguyen, Vu; Wang, Hongqin; Verdurand, Mathieu; Zavitsanou, Katerina

doi:10.1159/000335368

Cited by 2 publications

(2 citation statements)

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“…Purity (elemental analysis) >95 %. Blood brain barrier permeability of HU-210 in mouse (intraperitoneally, 0.1 mg per kilogram) was proved by Nguyen VH [ 36 ]. Cell-impermeable antagonist hemopressin, cell-permeable lipophilic antagonist AM251 and agonist THC were used in this experiment [ 7 ].…”

Section: Methodsmentioning

confidence: 99%

Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and it’s role in metabolic defects and neuronal apoptosis after TBI

Dai

et al. 2016

Mol Brain

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Metabolic defects and neuronal apoptosis initiated by traumatic brain injury (TBI) contribute to subsequent neurodegeneration. They are all regulated by mechanisms centered around mitochondrion. Type-1 cannabinoid receptor (CB1) is a G-protein coupled receptor (GPCR) enriched on neuronal plasma membrane. Recent evidences point to the substantial presence of CB1 receptors on neuronal mitochondrial outer membranes (mtCB1) and the activation of mtCB1 influences aerobic respiration via inhibiting mitochondrial cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/complex I pathway. The expression and role of neuronal mtCB1 under TBI are unknown. Using TBI models of cultured neurons, wild type and CB1 knockout mice, we found mtCB1 quickly upregulated after TBI. Activation of mtCB1 promoted metabolic defects accompanied with ATP shortage but protected neurons from apoptosis. Selective activation of plasma membrane CB1 showed no effects on neuronal metabolism and apoptosis. Activation of mtCB1 receptors inhibited mitochondrial cAMP/PKA/complex I and resulted in exacerbated metabolic defects accompanied with a higher ratio of ATP reduction to oxygen consumption decrease as well as neuronal apoptosis. Further research found the remarkable accumulation of protein kinase B (AKT) on neuronal mitochondria following TBI and the activation of mtCB1 upregulated mitochondrial AKT/complex V activity. Upregulation of mitochondrial AKT/complex V activity showed anti-apoptosis effects and alleviated ATP shortage in metabolic defects. Taken together, we have identified mtCB1 quickly upregulate after TBI and a dual role the mtCB1 might play in metabolic defects and neuronal apoptosis initiated by TBI: the inhibition of mitochondrial cAMP/PKA/complex I aggravates metabolic defects, energy insufficiency as well as neuronal apoptosis, but the coactivation of mitochondrial AKT/complex V mitigates energy insufficiency and neuronal apoptosis.

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Section: Methodsmentioning

confidence: 99%

Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and it’s role in metabolic defects and neuronal apoptosis after TBI

Dai

et al. 2016

Mol Brain

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“…However, most of the authors believe that CB 1 receptors are not located on dopaminergic neurons, but in striatal GABAergic projection neurons (striatonigral and striatopallidal pathways, respectively), in which they co‐localize with D 1 or D 2 receptors (Hermann et al ., ; Martín et al ., ). This may facilitate postsynaptic interactions between endocannabinoids and dopamine at the level of G‐protein/adenylyl cyclase signal transduction (Giuffrida et al ., ; Meschler and Howlett, ; Nguyen et al ., ). In addition, there is strong evidence supporting the formation of heteromers between CB 1 and D 2 receptors, and also adenosine A 2A receptors (see Ferré et al ., ; Brugarolas et al ., ).…”

Section: Cannabinoid–dopamine Interactions At the Basal Gangliamentioning

confidence: 97%

Cannabinoid–dopamine interactions in the physiology and physiopathology of the basal ganglia

Garcı́a

Palomo-Garo

Gómez‐Gálvez

et al. 2015

British J Pharmacology

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Endocannabinoids and their receptors play a modulatory role in the control of dopamine transmission in the basal ganglia. However, this influence is generally indirect and exerted through the modulation of GABA and glutamate inputs received by nigrostriatal dopaminergic neurons, which lack cannabinoid CB1 receptors although they may produce endocannabinoids. Additional evidence suggests that CB2 receptors may be located in nigrostriatal dopaminergic neurons, and that certain eicosanoid-related cannabinoids may directly activate TRPV1 receptors, which have been found in nigrostriatal dopaminergic neurons, thus allowing in both cases a direct regulation of dopamine transmission by specific cannabinoids. In addition, CB1 receptors form heteromers with dopaminergic receptors which provide another pathway to direct interactions between both systems, in this case at the postsynaptic level. Through these direct mechanisms or through indirect mechanisms involving GABA or glutamate neurons, cannabinoids may interact with dopaminergic transmission in the basal ganglia and this is likely to have important effects on dopamine-related functions in these structures (i.e. control of movement) and, particularly, on different pathologies affecting these processes, in particular, Parkinson's disease, but also dyskinesia, dystonia and other pathological conditions. The present review will address the current literature supporting these cannabinoid-dopamine interactions at the basal ganglia, with emphasis on aspects dealing with the physiopathological consequences of these interactions. DOI:10.1111/bph.13215 www.brjpharmacol.org Abbreviations REVIEW ARTICLE Overview of the endocannabinoid signalling system and its interaction with neurotransmitter systemsIt is well established that the endocannabinoid system, formed by different signalling lipids, the enzymes involved in their synthesis and degradation, and their target receptors, plays a modulatory function in important processes of the CNS. This includes the control of movement (see Fernández-Ruiz, 2009), learning and memory (see Zanettini et al., 2011), emotional behaviour (see McLaughlin and Gobbi, 2012), nociception (see Guindon and Hohmann, 2009), brain reward (see Solinas et al., 2008), feeding behaviour (see Kirkham, 2009) and emesis (see Parker et al., 2011), among others. This modulatory function is exerted through the ability of endocannabinoids and their receptors to participate in the retrograde signalling in different synapses located in those brain structures that regulate these processes (Castillo et al., 2012). This is facilitated by the presynaptic location of cannabinoid CB1 receptors, the key neuronal cannabinoid receptor type, that allow endocannabinoids to directly modulate the function of most of neurotransmitters including glutamate, GABA, opioid peptides, acetylcholine and 5-HT (see Heifets and Castillo, 2009;Kano et al., 2009). This function is particularly important in the case of glutamatergic and GABAergic synapses, in which, through welldefined proc...

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Differential Treatment Regimen-Related Effects of HU210 on CB<sub>1</sub> and D<sub>2</sub>-Like Receptor Functionality in the Rat Basal Ganglia

Cited by 2 publications

References 109 publications

Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and it’s role in metabolic defects and neuronal apoptosis after TBI

Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and it’s role in metabolic defects and neuronal apoptosis after TBI

Cannabinoid–dopamine interactions in the physiology and physiopathology of the basal ganglia

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