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The Endocannabinoid System and its Manifold Central Actions

  • M. Maccarrone
Reference work entry

Abstract:

Endocannabinoids are amides, esters, and ethers of long-chain polyunsaturated fatty acids, which act as endogenous agonists of cannabinoid receptors. Thus, they are able to mimic several pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive principle of Cannabis sativa preparations like hashish and marijuana. Anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol are the best-studied members of this new class of lipid mediators. It is now widely accepted that the biological activity of endocannabinoids is largely dependent on a “metabolic control,” which modulates the effects of these substances by modulating their in vivo concentration. Therefore, the metabolic routes that allow synthesis, transport, and degradation of endocannabinoids, and that altogether form the so-called “endocannabinoid system,” are the focus of intense research. This new system will be reviewed in the chapter, along with the molecular targets of endocannabinoids, and the signal transduction pathways triggered thereof. The aim of this update is also to put in a better perspective the cross-talks of endocannabinoids with other signaling molecules, and their implications for the manifold biological activities of these lipids within the central nervous system.

Keywords

Lipid Raft Fatty Acid Amide Hydrolase Vanilloid Receptor Fatty Acid Amide Hydrolase Inhibitor Fatty Acid Amide Hydrolase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations:

AC

adenylyl cyclase

AEA

anandamide (N-arachidonoylethanolamine)

2-AG

2-arachidonoylglycerol

AMT

AEA membrane transporter

ASK1

apoptosis signal-regulating kinase 1

BBM

bovine brain microvessels

CB1/2R

type 1/2 cannabinoid receptor

CNS

central nervous system

CPAE

calf pulmonary artery endothelium

CRE

cAMP response element

DAG

diacylglycerol

DAGL

diacylglycerol lipase

DSE

depolarization-induced suppression of excitation

DSI

depolarization-induced suppression of inhibition

E

estrogen (17β-estradiol)

ER

estrogen receptor

ERK

extracellular signal-regulated kinase

FAAH

fatty acid amide hydrolase

FAK

focal adhesion kinase

GABA

γ-aminobutyric acid

GPCR

G protein-coupled receptor

HPA

hypothalamic-pituitary-adrenal

HUVEC

human umbilical vein endothelial cells

JNK

c-Jun N-terminal kinase

LTD

long term depression

LTP

long term potentiation

MAFP

methyl-arachidonoyl fluorophosphonate

MAGL

monoacylglycerol lipase

MAPK

mitogen-activated protein kinase

MCD

methyl-β-cyclodextrin

mGluR

group I metabotropic glutamate receptor

NAAA

N-acylethanolamine-hydrolyzing acid amidase

NADA

N-arachidonoyldopamine

NAE

N-acylethanolamine

NAPE

N-acyl-phosphatidylethanolamine

NArPE

N-arachidonoylphosphatidylethanolamine

NAT

N-acyltransferase

NGF

nerve growth factor

NMDA

N-methyl-D-aspartate

NO

nitric oxide

NOS

nitric oxide synthase

OEA

N-oleoylethanolamine

P

progesterone

PEA

N-palmitoylethanolamine

PI3K

phosphatidylinositol 3-kinase

PKA/B

protein kinase A/B

PL A1/C/D

phospholipase A1C, D

PRL

prolactin

PVN

paraventricular nucleus

QSAR

quantitative structure-activity-relationship

RBE

rat brain endothelium

SEA

N-stearoylethanolamine

STAT

signal transducer and activator of transcription

TRPV1

transient receptor potential channel vanilloid receptor subunit 1

Notes

Acknowledgments

I wish to thank Prof. A. Finazzi-Agrò (Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata”) for continuing interest and support, and all colleagues who gave their valuable contribution over the years to the studies on the endocannabinoid system in the CNS. I also thank Dr. A. Paradisi for the excellent production of the artwork. This investigation was supported by Ministero dell’Istruzione, dell’Università e della Ricerca (COFIN 2002 and 2003), and by Fondazione TERCAS (Research Programs 2004 and 2005).

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© Springer Science+Business Media, LLC 2009

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  • M. Maccarrone

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