Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism.

Abstract:

BACKGROUND AND PURPOSE:Although CB(1) receptor activation evokes neuroprotection in response to cannabinoids, some cannabinoids have been reported to be peroxisome proliferator activated receptor (PPAR) ligands, offering an alternative protective mechanism. We have, therefore, investigated the ability of a range of cannabinoids to activate PPAR alpha and for N-oleoylethanolamine (OEA), an endogenous cannabinoid-like compound (ECL), to evoke neuroprotection. EXPERIMENTAL APPROACH:Assays of PPAR alpha occupancy and gene transactivation potential were conducted in cell-free and transfected HeLa cell preparations, respectively. In vivo estimates of PPAR alpha activation through fat mobilization and gene transcription were conducted in mice. Neuroprotection in vivo was investigated in wild-type and PPAR alpha gene-disrupted mice. KEY RESULTS:The ECLs OEA, anandamide, noladin ether and virodhamine were found to bind to the purified PPAR alpha ligand binding domain and to increase PPAR alpha-driven transcriptional activity. The high affinity synthetic CB(1/2) cannabinoid agonist WIN 55212-2 bound to PPAR alpha equipotently with the PPARalpha agonist fenofibrate, and stimulated PPARalpha-mediated gene transcription. The phytocannabinoid delta 9 tetrahydrocannabinol was without effect. OEA and WIN 55212-2 induced lipolysis in vivo, while OEA pre-treatment reduced infarct volume from middle cerebral artery occlusion in wild-type, but not in PPAR alpha-null mice. OEA treatment also led to increased expression of the NFkappa B-inhibitory protein, Ikappa B, in mouse cerebral cortex, while expression of the NFkappa B-regulated protein COX-2 was inhibited. CONCLUSIONS AND IMPLICATIONS:These data demonstrate the potential for a range of cannabinoid compounds, of diverse structures, to activate PPAR alpha and suggest that at least some of the neuroprotective properties of these agents could be mediated by nuclear receptor activation.

journal_name

Br J Pharmacol

authors

Sun Y,Alexander SP,Garle MJ,Gibson CL,Hewitt K,Murphy SP,Kendall DA,Bennett AJ

doi

10.1038/sj.bjp.0707478

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

734-43

issue

5

eissn

0007-1188

issn

1476-5381

pii

0707478

journal_volume

152

pub_type

杂志文章
  • Autoradiographic localization of beta-adrenoceptor subtypes in guinea-pig kidney.

    abstract::The distribution of beta-adrenoceptor subtypes in slide-mounted sections of guinea-pig kidney has been examined by the technique of in vitro labelling combined with autoradiography. Binding of (-)-[125I]-cyanopindolol (Cyp) to kidney sections equilibrated and dissociated slowly, was saturable and stereoselective with ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1985.tb08867.x

    authors: Lew R,Summers RJ

    更新日期:1985-06-01 00:00:00

  • Long-lasting activation of cation current by low concentration of endothelin-1 in mouse fibroblasts and smooth muscle cells of rabbit aorta.

    abstract::1. Recombinant human ETA receptors were expressed in a mouse fibroblast cell line (Ltk- cell) and functional coupling of the receptors with Ca2+ permeable channels at low concentrations of endothelin-1 (ET-1) was investigated using whole-cell recordings and monitoring the changes in intracellular free Ca2+ concentrati...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1995.tb16358.x

    authors: Enoki T,Miwa S,Sakamoto A,Minowa T,Komuro T,Kobayashi S,Ninomiya H,Masaki T

    更新日期:1995-06-01 00:00:00

  • Prostaglandin E(2) increases cyclic AMP and inhibits endothelin-1 production/secretion by guinea-pig tracheal epithelial cells through EP(4) receptors.

    abstract::Prostaglandin E(2) (PGE(2)) increased adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation in tracheal epithelial cells and concomitantly decreased the production/secretion of immunoreactive endothelin (irET). Naturally occurring prostanoids and selective and non-selective EP receptor agonists showed the foll...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703886

    authors: Pelletier S,Dubé J,Villeneuve A,Gobeil F Jr,Yang Q,Battistini B,Guillemette G,Sirois P

    更新日期:2001-03-01 00:00:00

  • Potentiation by aminopeptidase P of blood pressure response to bradykinin.

    abstract::We examined whether a specific aminopeptidase P (APP) inhibitor, apstatin, increases vasodepressor responses to bradykinin in anaesthetized rats, and whether it would augment blood pressure responses further after treatment with the angiotensin-converting enzyme inhibitor (ACEi), lisinopril. Apstatin doubled the maxim...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1995.tb14897.x

    authors: Kitamura S,Carbini LA,Carretero OA,Simmons WH,Scicli AG

    更新日期:1995-01-01 00:00:00

  • Effects of hydroxyethylrutosides on the permeability of microvessels in the frog mesentery.

    abstract::1. We have investigated the effects of a standardised mixture of hydroxyethylrutosides (HR, Venoruton), a mixture of five of its main components (M) and each of the five components separately (7-mono-HR, 7,4'-di-HR, 7,3',4'-tri-HR, 5,7,3',4'-tetra-HR and 7,3'4'-tri HQ) upon the permeability of single perfused capillar...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1993.tb13792.x

    authors: Kendall S,Towart R,Michel CC

    更新日期:1993-09-01 00:00:00

  • Endocannabinoid modulation by FAAH and monoacylglycerol lipase within the analgesic circuitry of the periaqueductal grey.

    abstract:BACKGROUND AND PURPOSE:Endogenous cannabinoids (endocannabinoids) in the periaqueductal grey (PAG) play a vital role in mediating stress-induced analgesia. This analgesic effect of endocannabinoids is enhanced by pharmacological inhibition of their degradative enzymes. However, the specific effects of endocannabinoids ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.12839

    authors: Lau BK,Drew GM,Mitchell VA,Vaughan CW

    更新日期:2014-12-01 00:00:00

  • Negative inotropic effects of endothelin-1 in mouse cardiomyocytes: evidence of a role for Na+-Ca2+ exchange.

    abstract::Endothelin-1 (ET-1) is a peptide hormone produced within the myocardium which may modulate myocardial contractility in a paracrine-autocrine fashion. In the majority of species, ET-1 has a direct positive inotropic effect on the myocardium that involves both increased myofilament Ca(2+) sensitivity and increased Ca(2+...

    journal_title:British journal of pharmacology

    pub_type: 评论,杂志文章

    doi:10.1038/sj.bjp.0707438

    authors: James AF

    更新日期:2007-10-01 00:00:00

  • Targeting the peptidase PCSK9 to reduce cardiovascular risk: Implications for basic science and upcoming challenges.

    abstract::LDL cholesterol (LDL-C) plays a central role in the progression of atherosclerosis. Statin therapy for lowering LDL-C reduces the risk of atherosclerotic cardiovascular disease and is the recommended first-line treatment for patients with high LDL-C levels. However, some patients are unable to achieve an adequate redu...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.14851

    authors: Nishikido T,Ray KK

    更新日期:2019-08-29 00:00:00

  • The effects of histamine on responses of the rabbit ear artery to electrical stimulation and to exogenous noradrenaline.

    abstract::1 The effects of a subconstrictor dose of histamine (9 x 10(-7) mol/l) on the responses of the isolated perfused ear artery of the rabbit to electrical stimulation (E.S.) and to exogenous noradrenaline (NA) were investigated.2 Both intraluminal (I/L) and extraluminal (E/L) histamine potentiated responses to E.S. and t...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1979.tb08684.x

    authors: Foldes A,Hall RC

    更新日期:1979-11-01 00:00:00

  • Diverse mechanisms underlying the regulation of ion channels by carbon monoxide.

    abstract::Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathologica...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.12760

    authors: Peers C,Boyle JP,Scragg JL,Dallas ML,Al-Owais MM,Hettiarachichi NT,Elies J,Johnson E,Gamper N,Steele DS

    更新日期:2015-03-01 00:00:00

  • Transparency in Research involving Animals: The Basel Declaration and new principles for reporting research in BJP manuscripts.

    abstract::This article discusses the background to the need for change in the reporting of experiments involving animals, including a report of a consensus meeting organised by the Basel Declaration Society and Understanding Animal Research UK that sought to Internationalise guidelines for reporting experiments involving animal...

    journal_title:British journal of pharmacology

    pub_type: 社论

    doi:10.1111/bph.12956

    authors: McGrath JC,McLachlan EM,Zeller R

    更新日期:2015-05-01 00:00:00

  • Endothelin-1 enhances oxidative stress, cell proliferation and reduces apoptosis in human umbilical vein endothelial cells: role of ETB receptor, NADPH oxidase and caveolin-1.

    abstract::1 Endothelin-1 (ET-1), an endothelium-derived vasoactive peptide, participates in the regulation of endothelial function through mechanisms that are not fully elucidated. This study examined the impact of ET-1 on oxidative stress, apoptosis and cell proliferation in human umbilical vein endothelial cells (HUVEC). HUVE...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706193

    authors: Dong F,Zhang X,Wold LE,Ren Q,Zhang Z,Ren J

    更新日期:2005-06-01 00:00:00

  • Effect of oral organic nitrates on expression and activity of vascular soluble guanylyl cyclase.

    abstract:BACKGROUND AND PURPOSE:The regulation of vascular soluble guanylyl cyclase (sGC) expression by nitric oxide (NO) is still under discussion. In vitro, NO has been shown to downregulate the expression of sGC but it is unclear if this mechanism is operative in vivo and occurs during nitrate treatment. EXPERIMENTAL APPROA...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/bjp.2008.269

    authors: Oppermann M,Dao VT,Suvorava T,Bas M,Kojda G

    更新日期:2008-10-01 00:00:00

  • Effect of alpha-trinositol on interstitial fluid pressure, oedema generation and albumin extravasation in experimental frostbite in the rat.

    abstract::1. The anti-inflammatory effect of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. Alpha-trinositol (40 mg kg body weight(-1)) was administered intravenously as a bolus b...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702442

    authors: Berg A,Aas P,Gustafsson T,Reed RK

    更新日期:1999-03-01 00:00:00

  • No proarrhythmic properties of the antibiotics Moxifloxacin or Azithromycin in anaesthetized dogs with chronic-AV block.

    abstract:BACKGROUND & PURPOSE:The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has not ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706900

    authors: Thomsen MB,Beekman JD,Attevelt NJ,Takahara A,Sugiyama A,Chiba K,Vos MA

    更新日期:2006-12-01 00:00:00

  • A patch clamp study of gamma-aminobutyric acid (GABA)-induced macroscopic currents in rat melanotrophs in cell culture.

    abstract::1. The macroscopic currents induced in cultured rat melanotrophs by exogenous gamma-aminobutyric acid (GABA) were analysed using the patch clamp recording technique. 2. Using various concentrations of intra- and extracellular chloride it was demonstrated that the conductance activated by GABA was chloride selective. S...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1987.tb11359.x

    authors: Kehl SJ,Hughes D,McBurney RN

    更新日期:1987-11-01 00:00:00

  • Peripheral inflammation affects modulation of nociceptive synaptic transmission in the spinal cord induced by N-arachidonoylphosphatidylethanolamine.

    abstract:BACKGROUND AND PURPOSE:Endocannabinoids play an important role in modulating spinal nociceptive signalling, crucial for the development of pain. The cannabinoid CB1 receptor and the TRPV1 cation channel are both activated by the endocannabinoid anandamide, a product of biosynthesis from the endogenous lipid precursor N...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13849

    authors: Nerandzic V,Mrozkova P,Adamek P,Spicarova D,Nagy I,Palecek J

    更新日期:2018-06-01 00:00:00

  • Pharmacokinetic and pharmacodynamic studies with two alpha-adrenoceptor antagonists, doxazosin and prazosin in the rabbit.

    abstract::The cardiovascular effects of doxazosin, a quinazoline derivative related to prasozin were investigated and compared to prazosin in the rabbit. Radioligand binding studies using rabbit cerebral membranes showed that both doxazosin and prazosin were roughly equipotent at displacing [3H]-prazosin from specific binding s...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1985.tb09437.x

    authors: Hamilton CA,Reid JL,Vincent J

    更新日期:1985-09-01 00:00:00

  • Activation of μ-opioid receptors by MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) and its fluorinated derivatives.

    abstract:BACKGROUND AND PURPOSE:A fluorinated derivative (2F-MT-45) of the synthetic μ-opioid receptor agonist MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) was recently identified in a seized illicit tablet. While MT-45 is a Class A drug, banned in a number of countries, nothing is known about the pharmacology of 2F-MT-...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.15064

    authors: Baptista-Hon DT,Smith M,Singleton S,Antonides LH,Nic Daeid N,McKenzie C,Hales TG

    更新日期:2020-08-01 00:00:00

  • DNA mismatch repair (MMR)-dependent 5-fluorouracil cytotoxicity and the potential for new therapeutic targets.

    abstract::The metabolism and efficacy of 5-fluorouracil (FUra) and other fluorinated pyrimidine (FP) derivatives have been intensively investigated for over fifty years. FUra and its antimetabolites can be incorporated at RNA- and DNA-levels, with RNA level incorporation provoking toxic responses in human normal tissue, and DNA...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1476-5381.2009.00423.x

    authors: Li LS,Morales JC,Veigl M,Sedwick D,Greer S,Meyers M,Wagner M,Fishel R,Boothman DA

    更新日期:2009-10-01 00:00:00

  • Ginsenosides-induced nitric oxide-mediated relaxation of the rabbit corpus cavernosum.

    abstract::1. Ginsenosides, the active ingredients extracted from Panax ginseng, have been shown to promote nitric oxide (NO) release in bovine aortic endothelial cells. Since the endothelial cells and the perivascular nerves in penile corpus cavernosum contain NO synthase and an NO-like substance has been shown to be released f...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1995.tb16313.x

    authors: Chen X,Lee TJ

    更新日期:1995-05-01 00:00:00

  • Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non-alcoholic fatty liver disease by up-regulating the FGF21/PGC-1α pathway.

    abstract:BACKGROUND AND PURPOSE:Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Astaxanthin (Ax) is a carotenoid, and beneficial effects of astaxanthin, including anti-oxidative, anti-inflammatory, and anti-tumour activity, have been identified. The p...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.15099

    authors: Wu L,Mo W,Feng J,Li J,Yu Q,Li S,Zhang J,Chen K,Ji J,Dai W,Wu J,Xu X,Mao Y,Guo C

    更新日期:2020-08-01 00:00:00

  • ADN-1184 a monoaminergic ligand with 5-HT(6/7) receptor antagonist activity: pharmacological profile and potential therapeutic utility.

    abstract:BACKGROUND AND PURPOSE:Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.12509

    authors: Kołaczkowski M,Mierzejewski P,Bieńkowski P,Wesołowska A,Newman-Tancredi A

    更新日期:2014-02-01 00:00:00

  • Betulinic acid inhibits endotoxin-stimulated phosphorylation cascade and pro-inflammatory prostaglandin E(2) production in human peripheral blood mononuclear cells.

    abstract:BACKGROUND AND PURPOSE:Betulinic acid (BA) is a naturally occurring triterpenoid widely distributed throughout the plant kingdom. We previously reported that BA inhibits lipopolysaccharide (LPS)-induced interleukin-6 production through modulation of nuclear factor κB (NF-κB) in human peripheral blood mononuclear cells ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2010.01112.x

    authors: Viji V,Helen A,Luxmi VR

    更新日期:2011-03-01 00:00:00

  • Studies on the mechanism by which tryptophan efflux from isolated synaptosomes is stimulated by depolarization.

    abstract::1. The efflux and influx of tryptophan across the synaptosomal plasma membrane has been studied under a variety of experimental conditions, in order to examine the mechanism by which depolarization enhances the efflux of tryptophan from superfused synaptosomes. 2. Efflux of [3H]-tryptophan from preloaded superfused sy...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1988.tb11440.x

    authors: Collard KJ,Wilkinson LS,Lewis DJ

    更新日期:1988-02-01 00:00:00

  • Beta-adrenoceptor subtype expression and function in rat white adipocytes.

    abstract::1. The pharmacological features of rat white adipocyte beta-adrenoceptor subtypes were investigated by saturation and beta-agonist competition studies with [3H]-CGP 12177 and by lipolysis induced by beta-agonists as well as their inhibition by CGP 20712A (selective beta 1-antagonist) and ICI 118551 (selective beta 2-a...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0700885

    authors: Germack R,Starzec AB,Vassy R,Perret GY

    更新日期:1997-01-01 00:00:00

  • Uptake, metabolism and release of (3H)-adrenaline by human platelets.

    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

    authors: Born GV,Smith JB

    更新日期:1970-08-01 00:00:00

  • Control of signalling efficacy by palmitoylation of the rat Y1 receptor.

    abstract::(1) We have investigated the properties of native and haemagglutinin (HA)-tagged neuropeptide Y (NPY) Y(1) receptors after mutation of the palmitoylation site Cys(337) to Ser or Ala. (2) In Chinese hamster ovary cells expressing similar receptor levels, the C337A mutation abolished incorporation of [(3)H]palmitic acid...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705276

    authors: Holliday ND,Cox HM

    更新日期:2003-06-01 00:00:00

  • The role of histamine receptors in the release of renin.

    abstract::1 The effect of intrarenal histamine, dimaprit (H2-agonist) and 2-(2-pyridyl) ethylamine (H1-agonist) on renin release was examined in anaesthetized dogs. 2 In dogs with intact kidneys, histamine and dimaprit administration resulted in renal vasodilatation, a two fold increase in urinary sodium excretion, and no chang...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1983.tb10495.x

    authors: Gerber JG,Nies AS

    更新日期:1983-05-01 00:00:00

  • The long-acting β2 -adrenoceptor agonist, indacaterol, enhances glucocorticoid receptor-mediated transcription in human airway epithelial cells in a gene- and agonist-dependent manner.

    abstract:BACKGROUND AND PURPOSE:Inhaled glucocorticoid (ICS)/long-acting β2 -adrenoceptor agonist (LABA) combination therapy is a recommended treatment option for patients with moderate/severe asthma in whom adequate control cannot be achieved by an ICS alone. Previously, we discovered that LABAs can augment dexamethasone-induc...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13087

    authors: Joshi T,Johnson M,Newton R,Giembycz MA

    更新日期:2015-05-01 00:00:00