Abstract:
:Extensive in vitro and in vivo studies have shown that cannabinoid drugs have neuroprotective properties and suggested that the endocannabinoid system may be involved in endogenous neuroprotective mechanisms. On the other hand, neurotoxic effects of cannabinoids in vitro and in vivo were also described. Several possible explanations for these dual, opposite effects of cannabinoids on cellular fate were suggested, and it is conceivable that various factors may determine the final outcome of the cannabinoid effect in vivo. In the current review, we focus on one of the possible reasons for the dual neuroprotective/neurotoxic effects of cannabinoids in vivo, namely, the opposite effects of low versus high doses of cannabinoids. While many studies reported neuroprotective effects of the conventional doses of cannabinoids in various experimental models for acute brain injuries, we have shown that a single administration of an extremely low dose of Δ(9) -tetrahydrocannabinol (THC) (3-4 orders of magnitude lower than the conventional doses) to mice induced long-lasting mild cognitive deficits that affected various aspects of memory and learning. These findings led to the idea that this low dose of THC, which induces minor damage to the brain, may activate preconditioning and/or postconditioning mechanisms and thus will protect the brain from more severe insults. Indeed, our recent findings support this assumption and show that a pre- or a postconditioning treatment with extremely low doses of THC, several days before or after brain injury, provides effective long-term cognitive neuroprotection. The future therapeutical potential of these findings is discussed.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Sarne Y,Asaf F,Fishbein M,Gafni M,Keren Odoi
10.1111/j.1476-5381.2011.01280.xsubject
Has Abstractpub_date
2011-08-01 00:00:00pages
1391-401issue
7eissn
0007-1188issn
1476-5381journal_volume
163pub_type
杂志文章,评审abstract::1. We investigated whether K(+) can act as an endothelium-derived hyperpolarizing factor (EDHF) in isolated small renal arteries of Wistar-Kyoto rats. 2. Acetylcholine (0.001 - 3 microM) caused relaxations that were abolished by removal of the endothelium. However, acetylcholine-induced relaxations were not affected b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703965
更新日期:2001-04-01 00:00:00
abstract::1. Strength-duration curves for threshold mechanical responses to single transmural stimuli were identical for rat and guinea-pig detrusor. In both species atropine had no effect on the curves, but the curves were shifted to the right by nerve blockade with tetrodotoxin (TTX), and by blockade of P2-purinoceptors with ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12956.x
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Humanized mice for the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ), termed PPARδ knock-in (PPARδ KI) mice, were generated for the investigation of functional differences between mouse and human PPARδ and as tools for early drug efficacy assessment. EXPERIMENTAL APPROACH...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01359.x
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abstract::Athletes attempt to improve performance with drugs that act on the beta-adrenergic system directly or indirectly. Of three beta-adrenoceptor (AR) subtypes, the beta(2)-AR is the main target in sport; they have bronchodilator and anabolic actions and enhance anti-inflammatory actions of corticosteroids. Although demons...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/bjp.2008.164
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abstract::1. Contractile responses to short trains of nerve stimulation have been characterized in small, medium and large arteries from the rat mesenteric circulation (5th - 6th, 2nd - 3rd and 1st order, respectively). In addition, sources of calcium for smooth muscle contraction have been investigated. 2. Nerve stimulation (1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703925
更新日期:2001-03-01 00:00:00
abstract::The control of ligand-gated receptors with light using photochromic compounds has evolved from the first handcrafted examples to accurate, engineered receptors, whose development is supported by rational design, high-resolution protein structures, comparative pharmacology and molecular biology manipulations. Photoswit...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14022
更新日期:2018-06-01 00:00:00
abstract::1. The modulation of L-type calcium channel current (ICa) by fendiline, a diphenylalkylamine type of calcium channel blocker was investigated on guinea-pig ventricular myocytes by use of the whole-cell patch-clamp technique. 2. Fendiline-induced block of ICa is accompanied by modulation of the channel kinetics in a co...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14308.x
更新日期:1992-05-01 00:00:00
abstract::1. The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on plasma lipoprotein (VLDL and LDL) concentration, composition and resistance to copper-induced oxidation has been studied in male Sprague-Dawley rats after a 15 day treatment. 2. Plasma triglyceride levels were reduced by CFB (41%) and BFB (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16710.x
更新日期:1996-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The cannabinoid receptor-mediated analgesic effects of 2-arachidonoylglycerol (2-AG) are limited by monoacylglycerol lipase (MAGL). 4-nitrophenyl 4-[bis (1,3-benzodioxol-5-yl) (hydroxy) methyl] piperidine-1-carboxylate (JZL184) is a potent inhibitor of MAGL in the mouse, though potency is reporte...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02179.x
更新日期:2012-12-01 00:00:00
abstract::1. NaF (10 mM) produced a 2-3 fold increase in adenylate cyclase activity in homogenates of NG108-15 cells incubated in the presence of 1 microM GTP. Higher concentrations of NaF suppressed adenylate cyclase activity. 2. In the presence of the adenosine receptor agonist 5'-(N-ethyl)-carboxamidoadenosine (NECA; 100 mic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb15786.x
更新日期:1990-06-01 00:00:00
abstract::1. We studied the effects of intracerebroventricular (i.c.v.) administration of prostanoid EP receptor ligands on vagally stimulated gastric acid secretion in rats anaesthetized with urethane. 2. Administration of misoprostol (EP3/EP2 receptor agonist) and sulprostone (EP3/EP1 receptor agonist) reduced vagally mediate...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15240.x
更新日期:1996-02-01 00:00:00
abstract::1. Column chromatography with Agarose A50m followed by Sephadex G100 was used to separate a fraction (extract II) in the molecular weight range 12,000 to 14,000 daltons from saline extracts of the sea anemone, Tealia felina. 2. Extract II inhibited histamine-induced contractions of the guinea-pig ileum and produced ha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb09115.x
更新日期:1981-02-01 00:00:00
abstract::1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries from female Wistar rats (220-250 g) following exposure to isotonic supraphysiological glucose solutions (20 and 45 mM, in physiological buffer, 2 h incubation). 2. Arteries incubated in 20 mM glucose d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17064.x
更新日期:1994-11-01 00:00:00
abstract::Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonar...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15248
更新日期:2020-09-01 00:00:00
abstract::1. Leptin, a pleiotropic hormone believed to regulate body weight, has recently been associated with inflammatory states and immune activity. Here we have studied the effect of leptin on expression of IFN-gamma-induced nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2), both prominent markers of macrophage act...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704903
更新日期:2002-11-01 00:00:00
abstract::1. Measurements were made of the uptake, metabolism and release of [(3)H]-adrenaline by human platelets in citrated plasma or in an artificial medium.2. Radioactive adrenaline was not taken up at 0-2 degrees C. At 37 degrees C there was a slow uptake which continued for at least 5 hours.3. About half of the radioactiv...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09903.x
更新日期:1970-08-01 00:00:00
abstract::The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1-yl)propyl]-5-ph...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb11138.x
更新日期:1986-09-01 00:00:00
abstract::1. Aqueous extracts of stratum corneum were found to cause histamine-like contractions of the guinea-pig ileum which were not antagonized by mepyramine, atropine or bromolysergic acid diethylamide.2. The compounds responsible for this contraction were isolated by chromatography and shown to be common amino acids, part...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb09581.x
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abstract::1. The effect of a single injection of the monoamine oxidase inhibitor, tranylcypromine, administered intravenously (20 mg/kg) or into the lateral cerebral ventricle (5-10 mg), on hypothalamic and rectal temperature, has been investigated.2. Intravenous tranylcypromine causes a significant rise in body temperature, wh...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb10594.x
更新日期:1970-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:MLN4924 prevents the formation of active cullin-RING ubiquitin ligase complexes and thus inhibits NF-κB signalling. Here, we evaluated the effects of this compound on monocytes and dendritic cells (DCs). EXPERIMENTAL APPROACH:Monocytes and DCs were challenged with TNF or LPS in the presence and ...
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更新日期:2015-03-01 00:00:00
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journal_title:British journal of pharmacology
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abstract:BACKGROUND AND PURPOSE:Depolarization-induced suppression of inhibition (DSI) and excitation (DSE) are two forms of cannabinoid CB(1) receptor-mediated inhibition of synaptic transmission, whose durations are regulated by endocannabinoid (eCB) degradation. We have recently shown that in cultured hippocampal neurons mon...
journal_title:British journal of pharmacology
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更新日期:2011-11-01 00:00:00
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更新日期:2003-07-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2008-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15875.x
更新日期:1995-05-01 00:00:00
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更新日期:2011-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Microglial phenotype and phagocytic activity are deregulated in Parkinson's disease (PD). PPARγ agonists are neuroprotective in experimental PD, but their role in regulating microglial phenotype and phagocytosis has been poorly investigated. We addressed it by using the PPARγ agonist MDG548. EXP...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2018-08-01 00:00:00