DOCSLIB.ORG

The Endocannabinoid System and Its Relevance for Nutrition

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Endocannabinoid System and Its Relevance for Nutrition NU30CH20-Maccarrone ARI 7 July 2010 4:52 The Endocannabinoid System and Its Relevance for Nutrition Mauro Maccarrone,1,2 Valeria Gasperi,3 Maria Valeria Catani,3 ThiAiDiep,4 Enrico Dainese,1 Harald S. Hansen,4 and Luciana Avigliano3 1Department of Biomedical Sciences, University of Teramo, Teramo, Italy; email: [email protected], [email protected] 2European Center for Brain Research (CERC)/Santa Lucia Foundation, Rome, Italy 3Department of Experimental Medicine and Biochemical Sciences, University of Rome, Tor Vergata, Rome, Italy; email: [email protected], [email protected], [email protected] 4Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark; email: [email protected], [email protected] Annu. Rev. Nutr. 2010. 30:423–40 Key Words The Annual Review of Nutrition is online at anandamide, 2-arachidonoylglycerol, diet, energy balance, food nutr.annualreviews.org intake, gastrointestinal pathologies, obesity This article’s doi: 10.1146/annurev.nutr.012809.104701 Abstract Copyright c 2010 by Annual Reviews. Endocannabinoids bind to cannabinoid, vanilloid, and peroxisome by Universidad de Costa Rica on 10/07/10. For personal use only. All rights reserved proliferator-activated receptors. The biological actions of these polyun- 0199-9885/10/0821-0423$20.00 saturated lipids are controlled by key agents responsible for their synthe- Annu. Rev. Nutr. 2010.30:423-440. Downloaded from www.annualreviews.org sis, transport and degradation, which together form an endocannabinoid system (ECS). In the past few years, evidence has been accumulated for a role of the ECS in regulating food intake and energy balance, both centrally and peripherally. In addition, up-regulation of the ECS in the gastrointestinal tract has a potential impact on inflammatory bowel dis- eases. In this review, the main features of the ECS are summarized in order to put in better focus our current knowledge of the nutritional relevance of endocannabinoid signaling and of its role in obesity, car- diovascular pathologies, and gastrointestinal diseases. The central and peripheral pathways that underlie these effects are discussed, as well as the possible exploitation of ECS components as novel drug targets for therapeutic intervention in eating disorders. 423 NU30CH20-Maccarrone ARI 7 July 2010 4:52 N-Arachidonoylethanolamine (anandamide, Contents AEA) and 2-arachidonoylglycerol (2-AG), the best studied members of fatty acid THE ENDOCANNABINOID amides (FAAs) and monoacylglycerols SYSTEM.......................... 424 (MAGs), respectively, are the most active Endocannabinoids . 424 eCBs as yet described (16). In addition, Metabolic Routes . 424 N-arachidonoyldopamine (NADA) has been Molecular Targets shown to behave as a cannabimimetic com- and Signaling Pathways . 425 pound (16), although its pharmacology is as yet Central and Peripheral Activities. 427 poorly understood. Other endogenous FAAs ENDOCANNABINOIDS IN are called endocannabinoid-like compounds FOOD............................ 427 because they do not activate CBRs but seem EFFECT OF DIET ON to have an entourage effect, i.e., they may ENDOCANNABINOID potentiate the activity of AEA or 2-AG at LEVELS.......................... 427 their receptors by inhibiting their degradation CONTROL OF ENERGY BALANCE (16). Among the latter substances are the anti- BY THE ENDOCANNABINOID inflammatory, anticonvulsant, and antiprolifer- SYSTEM.......................... 429 ative N-palmitoylethanolamine (PEA) (47), the CentralMechanisms............... 429 immunomodulator N-stearoylethanolamine, Peripheral Mechanisms . 430 which also induces apoptosis of glioma cells RELEVANCE OF THE (56), and notably the appetite-suppressor N- ENDOCANNABINOID oleoylethanolamine (OEA) (29). The chemical SYSTEM FOR OBESITY . 431 structures of 9-THC, relevant eCBs, PEA, RELEVANCE OF THE and OEA are shown in Figure 1. ENDOCANNABINOID SYSTEM FOR CARDIOVASCULAR DISEASES........................ 432 Metabolic Routes RELEVANCE OF THE AEA and 2-AG are produced on demand ENDOCANNABINOID through multiple biosynthetic pathways, SYSTEM FOR which include key agents such as the N- GASTROINTESTINAL acyl-phosphatidylethanolamines (NAPE)- PATHOLOGIES.................. 433 hydrolyzing phospholipase D (NAPE-PLD) THERAPEUTIC EXPLOITATION for AEA, PEA, and OEA (69), and the sn- by Universidad de Costa Rica on 10/07/10. For personal use only. OF ENDOCANNABINOID 1-specific diacylglycerol lipase for 2-AG (8). SYSTEM–ORIENTED DRUGS . 434 Other enzymes are also important, especially Annu. Rev. Nutr. 2010.30:423-440. Downloaded from www.annualreviews.org in the formation of AEA (16). The degradation Endocannabinoids of eCBs also occurs through multiple routes, (eCBs): a group of which include fatty acid amide hydrolase lipid-signaling molecules that include THE ENDOCANNABINOID (FAAH) (27) and monoacylglycerol lipase fatty acid amides and SYSTEM as major hydrolytic enzymes for AEA or monoacylglycerols. 2-AG, respectively (19). These biosynthetic or Endocannabinoids Anandamide (N- degradative enzymes allow metabolic control arachidonoylethano- In recent years, several natural lipids, named of the endogenous tone of eCBs, and hence lamine) and 2- arachidonoylglycerol endocannabinoids (eCBs), have been shown they regulate the biological activities of these are the prototype to bind to and activate cannabinoid re- substances. AEA, 2-AG, and their congeners, members of the two ceptors (CBRs), which are the molecular together with their target receptors and the families of targets of the Cannabis sativa active prin- purported endocannabinoid membrane trans- endocannabinoids ciple 9-tetrahydrocannabinol (9-THC). porters, form the endocannabinoid system 424 Maccarrone et al. NU30CH20-Maccarrone ARI 7 July 2010 4:52 Figure 1 Exogenous and endogenous cannabinoids. Chemical structures of the phytocannabinoid 9-THC, of biologically relevant endocannabinoids, and of the endocannabinoid-like compounds OEA and PEA are illustrated. (ECS). The identity and activity of some of and spleen and couples to G12 proteins in an the elements of the ECS are summarized in agonist- and tissue-dependent manner (85). Table 1. Recently, the orphan G-protein coupled re- CBRs: cannabinoid ceptor 119 (GPR119) also has been shown to receptors be activated by OEA, leading to stimulation of 9-THC: 9- by Universidad de Costa Rica on 10/07/10. For personal use only. Molecular Targets adenylyl cyclase through stimulatory G pro- tetrahydrocannabinol and Signaling Pathways teins (72). The activation of GPR119 could Annu. Rev. Nutr. 2010.30:423-440. Downloaded from www.annualreviews.org AEA: anandamide (N- AEA and 2-AG activate different signaling be, at least in part, responsible for the effects arachidonoylethano- pathways depending on the specific receptor of OEA on food intake, a hypothesis that is lamine) engaged (Table 2). To date, three CBRs have supported by the localization of the receptor 2-AG: 2- arachidonoylglycerol been shown to bind eCBs: type-1 (CB1R), in brain, pancreas, and gastrointestinal tract type-2 (CB2R), and a purported type-3 (CB3R (72). PEA: N- palmitoylethanolamine or GPR55). CB1R is mainly expressed in the AEA, but not 2-AG, is also an agonist central nervous system (CNS), but it is also of the transient receptor potential vanilloid 1 OEA: present in peripheral tissues, including adipose (TRPV1), which is the natural target of cap- N-oleoylethanolamine tissue, liver, and skeletal muscle (64), whereas saicin, the pungent ingredient of hot peppers NAPE-PLD: N-acyl- phosphatidylethano- CB2R is expressed in immune cells and in some (16). The AEA-TRPV1 interaction occurs at areas of CNS (38, 94, 99). CB R, which shares a cytosolic binding site and triggers protein lamines (NAPE)- 3 hydrolyzing kinase activation, intracellular Ca2+ increase, low sequence homology (10%–15%) with the phospholipase D other two CB receptors, has been found in brain mitochondrial uncoupling, and cytochrome c www.annualreviews.org • Endocannabinoids and Nutrition 425 NU30CH20-Maccarrone ARI 7 July 2010 4:52 Table 1 Elements of the endocannabinoid system that have been best characterized so far Member Description Function AEA Prototype member of fatty acid amides Bioactive lipid that acts at cannabinoid and noncannabinoid receptors in the central nervous system and in the periphery 2-AG Prototype member of Bioactive lipid that acts at cannabinoid and noncannabinoid receptors in monoacylglycerols the central nervous system and in the periphery EMT Endocannabinoid membrane So far a putative entity responsible for the transport of AEA and/or 2-AG transporter NAPE-PLD Biosynthetic enzyme Partly responsible for the biosynthesis of AEA DAGL Biosynthetic enzyme Mainly responsible for the biosynthesis of 2-AG FAAH Hydrolytic enzyme Mainly responsible for AEA degradation MAGL Hydrolytic enzyme Mainly responsible for 2-AG degradation CB1R Cannabinoid receptor Mainly targets of AEA and 2-AG CB2R CB3R? Cannabinoid receptor Novel target of endocannabinoids TRPV1 Vanilloid receptor Target of AEA and congeners PPARα Peroxisome proliferator-activated Targets of AEA, 2-AG, and congeners PPARγ receptor Abbreviations: 2-AG, 2-arachidonoylglycerol; AEA, arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol; CBRs, cannabinoid receptors; DAGL, diacylglycerol lipase; EMT, endocannabinoid membrane transporter; FAAH, fatty acid amide hydrolase; MAGL, monoacylglycerol lipase; NAPE-PLD, N-acyl-phosphatidylethanolamines-hydrolyzing phospholipase D; PPAR,
Load more

Recommended publications
  • Ultraprocessed Food: Addictive, Toxic, and Ready for Regulation
    nutrients Article Ultraprocessed Food: Addictive, Toxic, and Ready for Regulation Robert H. Lustig 1,2,3 1 Department of Pediatrics, University of California, San Francisco, CA 94143, USA; [email protected] 2 Institute for Health Policy Studies, University of California, San Francisco, CA 94143, USA 3 Department of Research, Touro University-California, Vallejo, CA 94592, USA Received: 27 September 2020; Accepted: 23 October 2020; Published: 5 November 2020 Abstract: Past public health crises (e.g., tobacco, alcohol, opioids, cholera, human immunodeficiency virus (HIV), lead, pollution, venereal disease, even coronavirus (COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCDs) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation—abuse, toxicity, ubiquity, and externalities (How does your consumption affect me?). To their credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCDs within their borders. This article also supplies scientific counters to food industry talking points, and sample intervention strategies, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.
    [Show full text]
  • The Endocannabinoid 2-Arachidonoylglycerol Negatively Regulates Habituation by Suppressing Excitatory Recurrent Network Activity
    3588 • The Journal of Neuroscience, February 20, 2013 • 33(8):3588–3601 Cellular/Molecular The Endocannabinoid 2-Arachidonoylglycerol Negatively Regulates Habituation by Suppressing Excitatory Recurrent Network Activity and Reducing Long-Term Potentiation in the Dentate Gyrus Yuki Sugaya,1 Barbara Cagniard,1 Maya Yamazaki,2 Kenji Sakimura,2 and Masanobu Kano1 1Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan and 2Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan Endocannabinoids are known to mediate retrograde suppression of synaptic transmission, modulate synaptic plasticity, and influence learning and memory. The 2-arachidonoylglycerol (2-AG) produced by diacylglycerol lipase ␣ (DGL␣) is regarded as the major endo- cannabinoid that causes retrograde synaptic suppression. To determine how 2-AG signaling influences learning and memory, we sub- jected DGL␣ knock-out mice to two learning tasks. We tested the mice using habituation and odor-guided transverse patterning tasks that are known to involve the dentate gyrus and the CA1, respectively, of the hippocampus. We found that DGL␣ knock-out mice showed significantly faster habituation to an odor and a new environment than wild-type littermates with normal performance in the transverse patterning task. In freely moving animals, long-term potentiation (LTP) induced by theta burst stimulation was significantly larger at perforantpath–granulecellsynapsesinthedentategyrusofDGL␣knock-outmice.Importantly,priorinductionofsynapticpotentiation
    [Show full text]
  • S42003-021-02488-1.Pdf
    ARTICLE https://doi.org/10.1038/s42003-021-02488-1 OPEN In situ imaging reveals disparity between prostaglandin localization and abundance of prostaglandin synthases ✉ Kyle D. Duncan 1,5, Xiaofei Sun 2,3,5, Erin S. Baker 4, Sudhansu K. Dey 2,3 & Ingela Lanekoff 1 Prostaglandins are important lipids involved in mediating many physiological processes, such as allergic responses, inflammation, and pregnancy. However, technical limitations of in-situ prostaglandin detection in tissue have led researchers to infer prostaglandin tissue dis- tributions from localization of regulatory synthases, such as COX1 and COX2. Herein, we apply a novel mass spectrometry imaging method for direct in situ tissue localization of 1234567890():,; prostaglandins, and combine it with techniques for protein expression and RNA localization. We report that prostaglandin D2, its precursors, and downstream synthases co-localize with the highest expression of COX1, and not COX2. Further, we study tissue with a conditional deletion of transformation-related protein 53 where pregnancy success is low and confirm that PG levels are altered, although localization is conserved. Our studies reveal that the abundance of COX and prostaglandin D2 synthases in cellular regions does not mirror the regional abundance of prostaglandins. Thus, we deduce that prostaglandins tissue localization and abundance may not be inferred by COX or prostaglandin synthases in uterine tissue, and must be resolved by an in situ prostaglandin imaging. 1 Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden. 2 Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA. 3 College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Fat Addiction: Psychological and Physiological Trajectory
    nutrients Discussion Fat Addiction: Psychological and Physiological Trajectory Siddharth Sarkar 1 , Kanwal Preet Kochhar 2 and Naim Akhtar Khan 3,* 1 Department of Psychiatry and National Drug Dependence Treatment Centre (NDDTC), All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India; [email protected] 2 Department of Physiology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India; [email protected] 3 Nutritional Physiology and Toxicology (NUTox), UMR INSERM U1231, University of Bourgogne and Franche-Comte (UBFC), 6 boulevard Gabriel, 21000 Dijon, France * Correspondence: [email protected]; Tel.: +33-3-80-39-63-12; Fax: + 33-3-80-39-63-30 Received: 9 October 2019; Accepted: 12 November 2019; Published: 15 November 2019 Abstract: Obesity has become a major public health concern worldwide due to its high social and economic burden, caused by its related comorbidities, impacting physical and mental health. Dietary fat is an important source of energy along with its rewarding and reinforcing properties. The nutritional recommendations for dietary fat vary from one country to another; however, the dietary reference intake (DRI) recommends not consuming more than 35% of total calories as fat. Food rich in fat is hyperpalatable, and is liable to be consumed in excess amounts. Food addiction as a concept has gained traction in recent years, as some aspects of addiction have been demonstrated for certain varieties of food. Fat addiction can be a diagnosable condition, which has similarities with the construct of addictive disorders, and is distinct from eating disorders or normal eating behaviors. Psychological vulnerabilities like attentional biases have been identified in individuals described to be having such addiction.
    [Show full text]
  • Lifestyle-Induced Metabolic Inflexibility and Accelerated Ageing Syndrome: Insulin Resistance, Friend Or Foe?
    Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe? Article Published Version Creative Commons: Attribution 3.0 (CC-BY) Nunn, A. V.W., Bell, J. D. and Guy, G. W. (2009) Lifestyle- induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe? Nutrition & Metabolism, 6 (16). ISSN 1743-7075 doi: https://doi.org/10.1186/1743-7075-6-16 Available at http://centaur.reading.ac.uk/35369/ It is advisable to refer to the publisher’s version if you intend to cite from the work. See Guidance on citing . To link to this article DOI: http://dx.doi.org/10.1186/1743-7075-6-16 Publisher: BioMed Central Ltd All outputs in CentAUR are protected by Intellectual Property Rights law, including copyright law. Copyright and IPR is retained by the creators or other copyright holders. Terms and conditions for use of this material are defined in the End User Agreement . www.reading.ac.uk/centaur CentAUR Central Archive at the University of Reading Reading’s research outputs online Nutrition & Metabolism BioMed Central Commentary Open Access Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe? Alistair VW Nunn*1, Jimmy D Bell1 and Geoffrey W Guy2 Address: 1Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, Du Cane Road, London, W12 OHS, UK and 2GW pharmaceuticals, Porton Down, Dorset, UK Email: Alistair VW Nunn* - [email protected]; Jimmy D Bell - [email protected]; Geoffrey W Guy - [email protected] * Corresponding author Published: 16 April 2009 Received: 12 August 2008 Accepted: 16 April 2009 Nutrition & Metabolism 2009, 6:16 doi:10.1186/1743-7075-6-16 This article is available from: http://www.nutritionandmetabolism.com/content/6/1/16 © 2009 Nunn et al; licensee BioMed Central Ltd.
    [Show full text]
  • Myeloid Innate Immunity Mouse Vapril2018
    Official Symbol Accession Alias / Previous Symbol Official Full Name 2810417H13Rik NM_026515.2 p15(PAF), Pclaf RIKEN cDNA 2810417H13 gene 2900026A02Rik NM_172884.3 Gm449, LOC231620 RIKEN cDNA 2900026A02 gene Abcc8 NM_011510.3 SUR1, Sur, D930031B21Rik ATP-binding cassette, sub-family C (CFTR/MRP), member 8 Acad10 NM_028037.4 2410021P16Rik acyl-Coenzyme A dehydrogenase family, member 10 Acly NM_134037.2 A730098H14Rik ATP citrate lyase Acod1 NM_008392.1 Irg1 aconitate decarboxylase 1 Acot11 NM_025590.4 Thea, 2010309H15Rik, 1110020M10Rik,acyl-CoA Them1, thioesterase BFIT1 11 Acot3 NM_134246.3 PTE-Ia, Pte2a acyl-CoA thioesterase 3 Acox1 NM_015729.2 Acyl-CoA oxidase, AOX, D130055E20Rikacyl-Coenzyme A oxidase 1, palmitoyl Adam19 NM_009616.4 Mltnb a disintegrin and metallopeptidase domain 19 (meltrin beta) Adam8 NM_007403.2 CD156a, MS2, E430039A18Rik, CD156a disintegrin and metallopeptidase domain 8 Adamts1 NM_009621.4 ADAM-TS1, ADAMTS-1, METH-1, METH1a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 1 Adamts12 NM_175501.2 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 12 Adamts14 NM_001081127.1 Adamts-14, TS14 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 14 Adamts17 NM_001033877.4 AU023434 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 17 Adamts2 NM_001277305.1 hPCPNI, ADAM-TS2, a disintegrin and ametalloproteinase disintegrin-like and with metallopeptidase thrombospondin
    [Show full text]
  • Calorie Restriction Is the Most Reasonable Anti-Ageing Intervention: a Meta-Analysis of Survival Curves
    www.nature.com/scientificreports OPEN Calorie restriction is the most reasonable anti-ageing intervention: a meta-analysis of Received: 5 January 2018 Accepted: 22 March 2018 survival curves Published: xx xx xxxx Yaru Liang1, Chang Liu2, Maoyang Lu1, Qiongye Dong2, Zimu Wang3, Zhuoran Wang1, Wenxiang Xiong1, Nannan Zhang1, Jiawei Zhou1, Qingfei Liu1, Xiaowo Wang2 & Zhao Wang1 Despite technological advances, the survival records from longevity experiments remain the most indispensable tool in ageing-related research. A variety of interventions, including medications, genetic manipulations and calorie restriction (CR), have been demonstrated to extend the lifespan of several species. Surprisingly, few systematic studies have investigated the diferences among these anti-ageing strategies using survival data. Here, we conduct a comprehensive and comparative meta-analysis of numerous published studies on Caenorhabditis elegans and Drosophila. We found that CR and genetic manipulations are generally more efective than medications at extending the total lifespan in both models, and CR can improve the ageing pattern of C. elegans. We further analysed the survival variation for diferent anti-ageing medications and determined that hypoglycaemic agents and antioxidants are advantageous despite only moderately increasing the overall lifespan; therefore, these two types of medications are promising CR mimetics. Analysis of genetic manipulations also indicated that the genes or pathways that extend lifespan in a healthier pattern are associated with CR. These results suggest that CR or CR mimetics may be the most reasonable and potentially benefcial anti-ageing strategy. Research on the biology of ageing has been conducted for centuries. Survival curves showing the surviving pro- portion of a population versus time are an intuitive means of illustrating the whole lifespan of a group of organ- isms and remain a key component of ageing research.
    [Show full text]
  • Cover Next Page > Cover Next Page >
    cover next page > Cover title: The Psychopharmacology of Herbal Medicine : Plant Drugs That Alter Mind, Brain, and Behavior author: Spinella, Marcello. publisher: MIT Press isbn10 | asin: 0262692651 print isbn13: 9780262692656 ebook isbn13: 9780585386645 language: English subject Psychotropic drugs, Herbs--Therapeutic use, Psychopharmacology, Medicinal plants--Psychological aspects. publication date: 2001 lcc: RC483.S65 2001eb ddc: 615/.788 subject: Psychotropic drugs, Herbs--Therapeutic use, Psychopharmacology, Medicinal plants--Psychological aspects. cover next page > < previous page page_i next page > Page i The Psychopharmacology of Herbal Medicine < previous page page_i next page > cover next page > Cover title: The Psychopharmacology of Herbal Medicine : Plant Drugs That Alter Mind, Brain, and Behavior author: Spinella, Marcello. publisher: MIT Press isbn10 | asin: 0262692651 print isbn13: 9780262692656 ebook isbn13: 9780585386645 language: English subject Psychotropic drugs, Herbs--Therapeutic use, Psychopharmacology, Medicinal plants--Psychological aspects. publication date: 2001 lcc: RC483.S65 2001eb ddc: 615/.788 subject: Psychotropic drugs, Herbs--Therapeutic use, Psychopharmacology, Medicinal plants--Psychological aspects. cover next page > < previous page page_ii next page > Page ii This page intentionally left blank. < previous page page_ii next page > < previous page page_iii next page > Page iii The Psychopharmacology of Herbal Medicine Plant Drugs That Alter Mind, Brain, and Behavior Marcello Spinella < previous page page_iii next page > < previous page page_iv next page > Page iv © 2001 Massachusetts Institute of Technology All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means (including photocopying, recording, or information storage and retrieval) without permission in writing from the publisher. This book was set in Adobe Sabon in QuarkXPress by Asco Typesetters, Hong Kong and was printed and bound in the United States of America.
    [Show full text]
  • Phosphatidylinositol-Specific Phospholipase C in Fetal Membranes and Uterine Decidua
    Phosphatidylinositol-specific Phospholipase C in Fetal Membranes and Uterine Decidua Gian Carlo Di Renzo, … , Paul C. MacDonald, John E. Bleasdale J Clin Invest. 1981;67(3):847-856. https://doi.org/10.1172/JCI110102. Research Article An assay procedure was developed in which phosphatidyl[2-3H]inositol was employed as substrate for the measurement of phosphatidylinositol-specific phospholipase C activity. Employing this assay, phosphatidylinositol-specific phospholipase C activity in human fetal membranes and uterine decidua was identified and characterized. The specific activity of this enzyme in amnion (4.4 μmol × mg−1 protein × h−1) was three times that in uterine decidua and more than five times that in chorion laeve. No difference was found between the specific activity of phosphatidylinositol-specific phospholipase C in placental amnion and that in reflected amnion. The products of phosphatidylinositol hydrolysis in short-term incubations were stoichiometric amounts of diacylglycerol and inositol-1,2-cyclic-phosphate plus inositol-1- phosphate. After longer periods of incubation, monoacylglycerol also was detected. Diacylglycerol lipase activity also was demonstrated in these tissues. More than 90% of phosphatidylinositol-specific phospholipase C activity of amnion tissue was recovered in the 105,000-g supernatant fraction, and optimal enzymatic activity in vitro was observed at pH 6.5-7.5 in the presence of Ca2+ (8 mM) and mercaptoethanol (4 mM). Phosphatidylinositol-specific phospholipase C activity was stimulated by fatty acids in low concentrations, but was inhibited by lysophosphatidylcholine and a variety of detergents. No effect of labor on the specific activity of phosphatidylinositol-specific phospholipase C in either fetal membranes or uterine decidua could be detected.
    [Show full text]
  • Stimulatory and Inhibitory Roles of Brain 2-Arachidonoylglycerol in Bombesin-Induced Central Activation of Adrenomedullary Outflow in Rats
    J Pharmacol Sci 121, 157 – 171 (2013) Journal of Pharmacological Sciences © The Japanese Pharmacological Society Full Paper Stimulatory and Inhibitory Roles of Brain 2-Arachidonoylglycerol in Bombesin-Induced Central Activation of Adrenomedullary Outflow in Rats Takahiro Shimizu1,*, Kenjiro Tanaka1, and Kunihiko Yokotani1 1Department of Pharmacology, School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan Received September 9, 2012; Accepted December 19, 2012 Abstract. 2-Arachidonoylglycerol (2-AG) is recognized as a potent endocannabinoid, which reduces synaptic transmission through cannabinoid CB1 receptors, and is hydrolyzed by mono- acylglycerol lipase (MGL) to arachidonic acid (AA), a cyclooxygenase substrate. We already reported that centrally administered MGL and cyclooxygenase inhibitors each reduced the intra- cerebroventricularly (i.c.v.) administered bombesin-induced secretion of adrenal catecholamines, while a centrally administered CB1-antagonist potentiated the response, indirectly suggesting bidirectional roles of brain 2-AG (stimulatory and inhibitory roles) in the bombesin-induced response. In the present study, we separately examined these bidirectional roles using 2-AG and 2-AG ether (2-AG-E) (stable 2-AG analog for MGL) in rats. 2-AG (0.5 μmol/animal, i.c.v.), but not 2-AG-E (0.5 μmol/animal, i.c.v.), elevated basal plasma catecholamines with JZL184 (MGL inhibitor)- and indomethacin (cyclooxygenase inhibitor)-sensitive brain mechanisms. 2-AG-E (0.1 μmol/animal, i.c.v.) effectively reduced the bombesin (1 nmol/animal, i.c.v.)-induced elevation of plasma catecholamines with rimonabant (CB1 antagonist)-sensitive brain mechanisms. Immuno- histochemical studies demonstrated the bombesin-induced activation of diacylglycerol lipase α (2-AG-producing enzyme)-positive spinally projecting neurons in the hypothalamic paraventricular nucleus, a control center of central adrenomedullary outflow.
    [Show full text]
  • Diacylglycerol Lipase-Alpha Regulates Hippocampal-Dependent Learning and Memory Processes in Mice
    This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. Research Articles: Behavioral/Cognitive Diacylglycerol lipase-alpha regulates hippocampal-dependent learning and memory processes in mice Lesley D Schurman1, Moriah C Carper1, Lauren V Moncayo1, Daisuke Ogasawara2, Karen Richardson1, Laikang Yu3, Xiaojie Liu3, Justin L. Poklis1, Qing-Song Liu3, Benjamin F Cravatt2 and Aron H Lichtman1,4 1Department of Pharmacology and Toxicology, Virginia Commonwealth University, 23298 2Department of Molecular Medicine, The Scripps Research Institute, 92037 3Department of Pharmacology and Toxicology, Medical College of Wisconsin, 53226 4Department of Medicinal Chemistry, Virginia Commonwealth University https://doi.org/10.1523/JNEUROSCI.1353-18.2019 Received: 27 May 2018 Revised: 24 April 2019 Accepted: 11 May 2019 Published: 24 May 2019 Author contributions: L.D.S., Q.-S.L., B.F.C., and A.H.L. designed research; L.D.S., M.C., L.V.M., K.R., L.Y., X.L., J.L.P., and Q.-S.L. performed research; L.D.S. and Q.-S.L. analyzed data; L.D.S. wrote the first draft of the paper; L.D.S., J.L.P., and Q.-S.L. wrote the paper; D.O. and B.F.C. contributed unpublished reagents/analytic tools; Q.-S.L., B.F.C., and A.H.L. edited the paper. Conflict of Interest: The authors declare no competing financial interests. This work was supported by the National Institutes of Health (NIH) [Grant NS093990 and DA039942] (to AHL), [Grant 1F31NS095628-01A1] (to LDS), [Grant DA035217] (to QSL), [Grant DA033760] (to BC), and Center grant [P30DA033934].
    [Show full text]