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The Endocannabinoid System and its Manifold Central Actions

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Handbook of Neurochemistry and Molecular Neurobiology

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.

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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

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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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  1. M. Maccarrone
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Medical Chemistry, Biochemistry and Biotechnology, Via Saldini 50, 20133, Milan, Italy

    Guido Tettamanti

  3. Department of Internal Medicine Section of Biochemistry, University of Perugia, via del Giochetto, 06122, Perugia, Italy

    Gianfrancesco Goracci

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Maccarrone, M. (2009). The Endocannabinoid System and its Manifold Central Actions. In: Lajtha, A., Tettamanti, G., Goracci, G. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30378-9_16

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