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Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Behavioral, biochemical and recent electrophysiological data have increasingly implicated the involvement of dopamine in the central actions of cannabinoid compounds. However, the site and mechanism by which cannabinoids stimulate dopamine systems has been somewhat controversial. Central opioid systems have also been suggested to play a role in some cannabinoid-induced behaviors as evidenced by their attenuation in the presence of the opioid antagonist naloxone. However, recent studies using the cannabinoid receptor-selective antagonist SR141716A suggest that the central actions of psychoactive cannabinoids are mediated principally through activation of CB1 receptors. Using single cell electrophysiological recordings in the rat we assessed the effects of both SR141716A and naloxone on delta9-tetrahydrocannabinol (THC)-induced activation of ventral tegmental dopamine neurons. While dopamine cell firing was dose-dependently increased following cumulative dosing with delta9-THC it was partially or completely inhibited following pretreatment with 0.5 and 2 mg/kg SR141716A, respectively. However, 1 and 10 mg/kg naloxone failed to alter the response to delta9-THC. These data provide the first evidence that delta9-THC-induced changes in mesolimbic dopamine neuronal activity are mediated by the CB1 cannabinoid receptor, but a causal link for the involvement of opioid systems could not be established.
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PMID:delta9-Tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors. 917 91

Previous studies indicate that the CB1 cannabinoid receptor antagonist, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-met hyl-1H-pyrazole-3-carboxamide HCl (SR141716A), inhibits the anandamide- and delta9-tetrahydrocannabinol- (THC) induced hypotension and bradycardia in anesthetized rats with a potency similar to that observed for SR141716A antagonism of THC-induced neurobehavioral effects. To further test the role of CB1 receptors in the cardiovascular effects of cannabinoids, we examined two additional criteria for receptor-specific interactions: the rank order of potency of agonists and stereoselectivity. A series of cannabinoid analogs including the enantiomeric pair (-)-11-OH-delta9-THC dimethylheptyl (+)-11-OH-delta9-THC dimethylheptyl were evaluated for their effects on arterial blood pressure and heart rate in urethane anesthetized rats. Six analogs elicited pronounced and long lasting hypotension and bradycardia that were blocked by 3 mg/kg of SR141716A. The rank order of potency was (-)-11-OH-delta9-THC dimethylheptyl > or = (-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]c yclohexan-1-ol > (-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]c yclohexan-1-ol > THC > anandamide > or = (-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]c yclohexan-1-ol, which correlated well with CB1 receptor affinity or analgesic potency (r = 0.96-0.99). There was no hypotension or bradycardia after palmitoylethanolamine or (+)-11-OH-delta9-THC dimethylheptyl. An initial pressor response was also observed with THC and anandamide, which was not antagonized by SR141716A. We conclude that the similar rank orders of potency, stereoselectivity and sensitivity to blockade by SR141716A indicate the involvement of CB1-like receptors in the hypotensive and bradycardic actions of cannabinoids, whereas the mechanism of the pressor effect of THC and anandamide remains unclear.
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PMID:Cannabinoid-induced hypotension and bradycardia in rats mediated by CB1-like cannabinoid receptors. 919 Aug 33

Intraperitoneal injection of delta9-THC (7.5 mg/kg) in rats made tolerant to morphine by s.c. implantation of morphine pellets had a much greater analgesic effect than in placebo pellet plus delta9-THC treatment. To investigate whether this was due to some change in cannabinoid receptor levels and/or expression induced by chronic morphine, we designed this autoradiographic binding study coupled with in situ hybridization on sagittal sections of the treated rat brains. Binding showed a significant increase in CB1 receptor density (15%) specifically in the caudate-putamen, in parallel with a significant enhancement of CB1 mRNA in the same area (20%). We suggest that morphine chronic treatment leads to a functional modulation between the opioid and cannabinoid systems at least for analgesia in a specific area, in this case the striatum.
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PMID:Modulation of rat brain cannabinoid receptors after chronic morphine treatment. 935 46

Cannabinoids are a class of compound found in marijuana which have been known for their therapeutic and psychoactive properties for at least 4000 years. Isolation of the active principle in marijuana, delta9-THC, provided the lead structure in the development of highly potent congeners which were used to probe for the mechanism of marijuana action. Cannabinoids were shown to bind to selective binding sites in brain tissue thereby regulating second messenger formation. Such studies led to the cloning of three cannabinoid receptor subtypes, CB1, CB2, and CB1A all of which belong to the superfamily of G protein-coupled plasma membrane receptors. Analogous to the discovery of endogenous opiates, isolation of cannabinoid receptors provided the appropriate tool to isolate an endogenous cannabimimetic eicosanoid, anandamide, from porcine brain. Recent studies indicate that anandamide is a member of a family of fatty acid ethanolamides that may represent a novel class of lipid neurotransmitters. This review discusses recent progress in cannabinoid research with a focus on the receptors for delta9-THC, their coupling to second messenger responses, and the endogenous lipid cannabimimetic, anandamide.
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PMID:Cannabinoid receptors and their endogenous agonist, anandamide. 956 94

Cognitive impairments during psychotic episodes are assumed to be caused not only by one single putative classical neurotransmitter dysfunction but also to be due to an impaired equilibrium of the interaction between different neurobiological generators of cognitive processes. Here, the perceptual abnormalities induced by psychotogenic agents play a major role as tools for understanding model psychoses. The recently discovered cannabinoid receptor system with its endogenous ligand anandamide can be regarded as an extremely relevant regulation system, a dysfunctionality of which may explain at least one subtype of endogenous psychoses. The present paper discusses the possible associations between the endogenous anandamide/cannabinoid system and schizophrenic psychoses. Neuropsychological experiments with the 3-D inversion paradigm were performed in healthy volunteers intoxicated with delta9-Tetrahydrocannabinol (delta9-THC). The 3-D inversion paradigm represents a visual illusion of binocular depth perception. Such an inversion occurs in many cases, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. It is assumed that cognitive factors override the binocular disparity cues of stereopsis. We tested the hypothesis that, during psychotic and related prepsychotic states, the human CNS is unable to correct implausible perceptual hypotheses. Our study provides evidence of strong similarities between data acquired from patients, suffering from productive schizophrenic psychoses and delta9-THC-intoxicated healthy volunteers, as concerns disturbances in the internal regulation of perceptual processes.
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PMID:Cannabinoid/anandamide system and schizophrenia: is there evidence for association? 975 42

delta9-Tetrahydrocannabinol (THC), the major active component of marijuana, induced apoptosis in C6.9 glioma cells, as determined by DNA fragmentation and loss of plasma membrane asymmetry. THC stimulated sphingomyelin hydrolysis in C6.9 glioma cells. THC and N-acetylsphingosine, a cell-permeable ceramide analog, induced apoptosis in several transformed neural cells but not in primary astrocytes or neurons. Although glioma C6.9 cells expressed the CBI cannabinoid receptor, neither THC-induced apoptosis nor THC-induced sphingomyelin breakdown were prevented by SR141716, a specific antagonist of that receptor. Results thus show that THC-induced apoptosis in glioma C6.9 cells may rely on a CBI receptor-independent stimulation of sphingomyelin breakdown.
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PMID:Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. 977 84

The effects of cannabinoids on metabolic pathways and signal transduction systems were studied in primary cultures of rat astrocytes. Delta9-Tetrahydrocannabinol (THC), the major active component of marijuana, increased the rate of glucose oxidation to CO2 as well as the rate of glucose incorporation into phospholipids and glycogen. These effects of THC were mimicked by the synthetic cannabinoid HU-210, and prevented by forskolin, pertussis toxin, and the CB1 receptor antagonist SR 141716. THC did not affect basal cAMP levels but partially antagonized the forskolin-induced elevation of intracellular cAMP concentration. THC stimulated p42/p44 mitogen-activated protein kinase (MAPK) activity, Raf-1 phosphorylation, and Raf-1 translocation to the particulate cell fraction. In addition, the MAPK inhibitor PD 098095 and the phosphoinositide 3-kinase inhibitors wortmannin and LY 294002 were able to antagonize the THC-induced stimulation of glucose oxidation to CO2, phospholipid synthesis and glycogen synthesis. The possible involvement of sphingomyelin breakdown in the metabolic effects of THC was studied subsequently. THC produced a rapid stimulation of sphingomyelin hydrolysis that was concomitant to an elevation of intracellular ceramide levels. This effect was prevented by SR 141716. Moreover, the cell-permeable ceramide analog D-erythro-N-octanoylsphingosine, as well as exogenous sphingomyelinase, were able in turn to stimulate MAPK activity, to increase the amount of Raf-1 bound to the particulate cell fraction, and to stimulate glucose metabolism. The latter effect was prevented by PD 098059 and was not additive to that exerted by THC. Results thus indicate that THC produces a cannabinoid receptor-mediated stimulation of astrocyte metabolism that seems to rely on sphingomyelin hydrolysis and MAPK stimulation.
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PMID:Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the Delta9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes. 980 18

The effects of cannabinoids on ketogenesis in primary cultures of rat astrocytes were studied. Delta9-Tetrahydrocannabinol (THC), the major active component of marijuana, produced a malonyl-CoA-independent stimulation of carnitine palmitoyltransferase I (CPT-I) and ketogenesis from [14C]palmitate. The THC-induced stimulation of ketogenesis was mimicked by the synthetic cannabinoid HU-210 and was prevented by pertussis toxin and the CB1 cannabinoid receptor antagonist SR141716. Experiments performed with different cellular modulators indicated that the THC-induced stimulation of ketogenesis was independent of cyclic AMP, Ca2+, protein kinase C, and mitogen-activated protein kinase (MAPK). The possible involvement of ceramide in the activation of ketogenesis by cannabinoids was subsequently studied. THC produced a CB1 receptor-dependent stimulation of sphingomyelin breakdown that was concomitant to an elevation of intracellular ceramide levels. Addition of exogenous sphingomyelinase to the astrocyte culture medium led to a MAPK-independent activation of ketogenesis that was quantitatively similar and not additive to that exerted by THC. Furthermore, ceramide activated CPT-I in astrocyte mitochondria. Results thus indicate that cannabinoids stimulate ketogenesis in astrocytes by a mechanism that may rely on CB1 receptor activation, sphingomyelin hydrolysis, and ceramide-mediated activation of CPT-I.
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PMID:The stimulation of ketogenesis by cannabinoids in cultured astrocytes defines carnitine palmitoyltransferase I as a new ceramide-activated enzyme. 1009 87

Delta9-Tetrahydrocannabinol (Delta9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Delta9-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CB1 mutant mice. In contrast, we still found Delta9-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta9-THC administration. Thus, most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor.
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PMID:Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. 1031 80

Peripheral administration of cannabinoid CB1 receptor agonists to laboratory rats induce a brief rise in plasma prolactin (PRL) levels followed by a prolonged decrease in PRL secretion from the pituitary. While the inhibitory component of this biphasic response depends on the cannabinoid-induced activation of dopamine release from hypothalamic terminals located in the median eminence, the neurobiological mechanisms underlying the activation phase of PRL release remains to be explained. In the present study the possible direct effect of the cannabinoid receptor agonist delta9-Tetrahydrocannabinol (THC) on prolactin secretion and cAMP accumulation was examined in anterior pituitary cultures. THC (0.1 and 1 microM) increased cAMP levels, and induced PRL release (1 and 10 mu). THC did not affect vasoactive intestinal peptide (VIP, 0.5 microM) induced cAMP accumulation in pituitary cultures, showing additive effects at THC 1 microM concentration. However, THC did prevent VIP-dependent increases in prolactin secretion. These results indicate that THC, through a direct pituitary action, activates both the synthesis of cAMP and PRL release and interferes with intracellular mechanisms involved in PRL secretion by VIP. These actions could be mediated through cannabinoid CB1 receptors which were found to be present in anterior pituitary cells, including lactotrophs, as revealed by immunocytochemistry with a specific polyclonal antibody raised against the CB1 receptor protein.
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PMID:Effects of delta9-THC on VIP-induced prolactin secretion in anterior pituitary cultures: evidence for the presence of functional cannabinoid CB1 receptors in pituitary cells. 1054 94


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