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

The present work was undertaken to study the metabolic response of mouse spleen lymphocytes to physiologically relevant doses of delta9-tetrahydrocannabinol (THC), the major active component of marijuana. At those concentrations (i.e. nanomolar range), THC induced a 2-2.5-fold stimulation of both glucose oxidation to CO2 and phospholipid synthesis from glucose. This stimulation was (i) dose-dependent up to 1 microM THC, (ii) mimicked by the synthetic cannabinoid HU-210, (iii) prevented by forskolin and pertussis toxin, and (iv) unaffected by the CB1 receptor antagonist SR141716A. THC was also able to antagonize the forskolin-induced elevation of intracellular cAMP concentration. In contrast, at non-physiological, cytotoxic doses (i.e. micromolar range) THC markedly depressed glucose metabolism in lymphocytes by a cannabinoid receptor-independent pathway. Results thus indicate that physiologically relevant doses of THC induce a metabolic stimulation of lymphocytes that seems to be mediated by a cannabinoid receptor-dependent pathway.
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PMID:Metabolic stimulation of mouse spleen lymphocytes by low doses of delta9-tetrahydrocannabinol. 912 26

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 evidence suggests that the endogenous cannabinoid system could emerge and be operative early during brain development. In the present study, we have explored the distribution of specific binding for cannabinoid receptors in rat brain at gestational day 21 (GD21), postnatal days 5 (PND5) and 30 (PND30), and at adult age (> 70 days after birth) by using autoradiography with [3H]CP-55,940. Our results indicated that specific binding for cannabinoid receptors can be detected in the brain of rat fetuses at GD21 in the classic areas that contain these receptors in adulthood-in particular, in the cerebellum and the hippocampus and, to a lesser extent, in the basal ganglia, several limbic structures, and cerebral cortex. The density of cannabinoid receptors in all these structures increased progressively at all postnatal ages studied until reaching the classical adult values in 70-day-old animals. Interestingly, cannabinoid receptor binding can also be detected at GD21 in regions, in which they are scarcely distributed or not located in the adult brain and that have the particularity of all being enriched in neuronal fibers. Among these were the corpus callosum, anterior commissure, stria terminalis, fornix, white matter areas of brainstem, and others. This atypical location was quantitatively high at GD21, tended to wane at PND5, and practically disappeared at PND30 and in adulthood, with the only exception being the anterior commissure, which exhibited a moderate density for cannabinoid receptors. Moreover, the binding of [3H]CP-55,940 to cannabinoid receptors in the white matter regions at GD21 seems to be functional and involves a GTP-binding protein-mediated mechanism. Thus, the activation of these receptors with an agonist such as WIN-55,212-2 increased the binding of [35S]-guanylyl-5'-O-(gamma-thio)-triphosphate, measured by autoradiography, in the corpus callosum and white matter areas of brainstem of fetuses at GD21. This increase was reversed by coincubation of WIN-55,212-2 with SR141716, a cannabinoid receptor antagonist. As this antagonist is specific for the cerebral cannabinoid receptor subtype, called CB1, we can assert that the signal found for cannabinoid receptor binding in the fetal and early postnatal brain likely corresponds to this receptor subtype. Collectively, all these data suggest the existence of a transient period of the brain development in the rat, around the last days of the fetal period and the first days of postnatal life, in which CB1 receptors appear located in neuronal fiber-enriched areas. During this period, CB1 receptors would be already functional acting through a GTP-binding protein-mediated mechanism. After this transient period, they progressively acquire the pattern of adult distribution. All this accounts for a specific role of the endogenous cannabinoid system in brain development.
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PMID:Atypical location of cannabinoid receptors in white matter areas during rat brain development. 918 20

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

Using the polymerase chain reaction with degenerate primers to identify novel G-protein-coupled receptors of the rat alveolar Type II cell, we identified sequences expressed by the Type II cell identical to the sequence of the rat brain cannabinoid receptor (CB1). The use of Northern blot analysis to examine expression of CB1 mRNA in rat tissues revealed differences between the brain and lung. While rat brain expressed a 6.0 kb mRNA as previously described, rat lung expressed mRNA of 4.5 and 6.0 kb. Isolated lung alveolar Type II cells also expressed mRNA of 4.5 and 6.0 kb as determined by Northern analysis. However, only freshly isolated Type II cells contained cannabinoid receptor mRNA. Reverse transcriptase-polymerase chain reaction (RT-PCR) failed to detect CB1 mRNA in Type II cells maintained in culture for 1 or 2 days. We next determined developmental changes in lung CB1 mRNA expression using semi-quantitative RT-PCR. CB1 expression was detected as early as gestational day 16 in rat lung and mRNA levels increased to fetal day 20 before birth, before declining to adult levels. Fetal rat lung explants were utilized to further examine the ontogeny and hormonal effects on CB1 mRNA expression. Hydrocortisone induced a dose-dependent expression in 15-day and 18-day explants, similar to previous results for surfactant-associated proteins. Our results demonstrate expression of CB1 mRNA in rat alveolar Type II cells and rat lung. This expression is ontogenically and hormonally regulated, with maximal expression noted just prior to birth in rat lung. Since CB1 mRNA is only expressed in freshly isolated Type II cells, CB1 may be useful as a Type II cell marker.
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PMID:Expression of a brain-type cannabinoid receptor (CB1) in alveolar Type II cells in the lung: regulation by hydrocortisone. 920 May 64

Cannabinoids act at the CB1 receptor to inhibit adenylate cyclase activity via a pertussis toxin-sensitive G-protein. Within the striatum, CB1 receptors have been shown to be localized on the same neurons as Gi-coupled dopamine D2 receptors. In this study we have examined the interactions of CB1 and D2 receptors on adenylate cyclase. In striatal neurons in primary culture, both the CB1 receptor agonist [3-(1, 1-dimethylheptyl)-11-hydroxy-Delta8tetrahydrocannabinol] (HU210) and the D2 receptor agonist quinpirole inhibited forskolin-stimulated cAMP accumulation when applied separately. In contrast, HU210 and quinpirole in combination augmented cAMP accumulation. This augmentation was blocked by the CB1 receptor antagonist SR141716A or the D2 antagonist sulpride. Pertussis toxin treatment of striatal neurons prevented the inhibition of cAMP accumulation by D2 receptors but unmasked a cannabinoid receptor-mediated stimulatory effect on cAMP accumulation. The cannabinoid receptor-stimulated accumulation of cAMP was blocked in a concentration-dependent manner by SR141716A, suggesting that the response was regulated through the CB1 receptor. Similar augmentation of cAMP accumulation after pertussis toxin treatment was observed in Chinese hamster ovary (CHO) cells transfected with, and stably expressing, the CB1 receptor. This stimulation of cAMP was not Ca2+-sensitive and was unaffected by a range of protein kinase inhibitors. Treatment of the pertussis toxin-treated cells with cholera toxin before CB1 receptor activation amplified the stimulatory pathway, suggesting that this response was mediated through a Gs-type G-protein. Stimulation of cAMP accumulation was not observed after pertussis toxin treatment of CHO cells expressing the human CB2 receptor, suggesting that this novel signaling pathway is unique to the cannabinoid CB1 receptor.
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PMID:Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. 920 17

The effects of two cannabinoid receptor agonists, R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4- benzoxazin-yl]-(1-naphthalenyl)-methanone (WIN 55,212-2) and (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydr oxypropyl)-cyclohexanol (CP-55,940), were studied on (i) the vasopressor response elicited in pithed rats by electrical stimulation of the sympathetic outflow and (ii) the release of 3H-noradrenaline and the vasoconstriction elicited in isolated rat tail arteries by transmural electrical stimulation. In pithed rats, the electrical (1 Hz for 10 s) stimulation of the preganglionic sympathetic nerve fibres increased diastolic blood pressure by about 30 mmHg. This neurogenic vasopressor response (which under the conditions of our study was almost exclusively due to the release of catecholamines) was decreased by WIN 55-212,2 and CP-55,940 in a dose-dependent manner (inhibition by WIN 55,212-2 and CP-55,940, 0.1 micromol/kg each, about 25-30%). The inhibition was identical in adrenalectomized rats and in animals with intact adrenals. The inhibitory action of WIN 55,212-2 and CP-55,940 was abolished by a dose of 0.03 micromol/kg of the CB1 receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazo le-carboxamide (SR 141716), which, by itself, had no effect. WIN 55,212-2, CP-55,940 and SR 141716 failed to affect the vasopressor response to exogenous noradrenaline (1 nmol/kg), which also increased diastolic blood pressure by about 30 mmHg. In isolated rat tail arteries, the electrically (0.4 Hz) evoked tritium overflow and vasoconstriction were not modified by WIN 55,212-2 and CP-55,940 (1 micromol/l each). In conclusion, the neurogenic vasopressor response in the pithed rat can be modulated via cannabinoid CB1 receptors probably located presynaptically on the postganglionic sympathetic nerve fibres innervating resistance vessels.
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PMID:Cannabinoid CB1 receptor-mediated inhibition of the neurogenic vasopressor response in the pithed rat. 927 25

SR 141716, a selective central CB1 cannabinoid receptor antagonist, markedly and selectively reduces sucrose feeding and drinking as well as neuropeptide Y-induced sucrose drinking in rats. SR 141716 also decreases ethanol consumption in C57BL/6 mice. In contrast, blockade of CB1 receptors only marginally affects regular chow intake or water drinking. The active doses of SR 141716 (0.3-3 mg/kg) are in the range known to antagonize the characteristic effects induced by cannabinoid receptor agonists. These results suggest for the first time that endogenous cannabinoid systems may modulate the appetitive value of sucrose and ethanol, perhaps by affecting the activity of brain reward systems.
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PMID:Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. 927 66

Using the endogenous cannabinoid receptor agonist anandamide, the synthetic agonist CP 55940 [[1alpha,2beta(R)5alpha]-(-)-5-(1,1-dimethylheptyl+ ++)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol], and the specific antagonist SR 141716 [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride], second messenger activation of the central cannabinoid receptor (CB1) was examined in rat striatal and cortical slices. The effects of these cannabinoid ligands on electrically evoked dopamine (DA) release from [3H] dopamine-prelabelled striatal slices were also investigated. CP 55940 (1 microM) and anandamide (10 microM) caused significant reductions in forskolin-stimulated cyclic AMP accumulation in rat striatal slices, which were reversed in the presence of SR 141716 (1 microM). CP 55940 (1 microM) had no effect on either KCl- or neurotransmitter-stimulated 3H-inositol phosphate accumulation in rat cortical slices. CP 55940 and anandamide caused significant reductions in the release of dopamine after electrical stimulation of [3H]dopamine-prelabelied striatal slices, which were antagonised by SR 141716. SR 141716 alone had no effect on electrically evoked dopamine release from rat striatal slices. These data indicate that the CB1 receptors in rat striatum are negatively linked to adenylyl cyclase and dopamine release. That the CB1 receptor may influence dopamine release in the striatum suggests that cannabinoids play a modulatory role in dopaminergic neuronal pathways.
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PMID:Influence of cannabinoids on electrically evoked dopamine release and cyclic AMP generation in the rat striatum. 928 35

The endogenous cannabinoid, anandamide, has been suggested as an endothelium-derived hyperpolarizing factor (EDHF). We found that anandamide-evoked relaxation in isolated segments of rat mesenteric artery was associated with smooth muscle hyperpolarization. However, although anandamide-evoked relaxation was inhibited by either charybdotoxin (ChTX) or iberiotoxin, inhibition of the relaxation to EDHF required a combination of ChTX and apamin. The relaxations induced by either anandamide or EDHF were not inhibited by the cannabinoid receptor (CB1) antagonist SRI41716A, or mimicked by selective CB1 agonists. Thus, anandamide appears to cause smooth muscle relaxation via a CB1 receptor-independent mechanism and cannabinoid receptor activation apparently does not contribute to EDHF-mediated relaxation in this resistance artery.
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PMID:Evidence that anandamide and EDHF act via different mechanisms in rat isolated mesenteric arteries. 928 82


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