Linked Life Data

11408519

Source:http://linkedlifedata.com/resource/pubmed/id/11408519

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-6-15
pubmed:abstractText
The endocannabinoids, a family of endogenous lipids that activate cannabinoid receptors, are released from cells in a stimulus-dependent manner by cleavage of membrane lipid precursors. After release, the endocannabinoids are rapidly deactivated by uptake into cells and enzymatic hydrolysis. Endocannabinoid reuptake occurs via a carrier-mediated mechanism, which has not yet been molecularly characterized. Endocannabinoid reuptake has been demonstrated in discrete brain regions and in various tissues and cells throughout the body. Inhibitors of endocannabinoid reuptake include N-(4-hydroxyphenyl)-arachidonylamide (AM404), which blocks transport with IC50 (concentration necessary to produce half-maximal inhibition) values in the low micromolar range. AM404 does not directly activate cannabinoid receptors or display cannabimimetic activity in vivo. Nevertheless, AM404 increases circulating anandamide levels and inhibits motor activity, an effect that is prevented by the CB1 cannabinoid antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A). AM404 also reduces behavioral responses to dopamine agonists and normalizes motor activity in a rat model of attention deficit hyperactivity disorder. The endocannabinoids are hydrolyzed by an intracellular membrane-bound enzyme, termed anandamide amidohydrolase (AAH), which has been molecularly cloned. Several fatty acid sulfonyl fluorides inhibit AAH activity irreversibly with IC50 values in the low nanomolar range and protect anandamide from deactivation in vivo. alpha-Keto-oxazolopyridines inhibit AAH activity with high potency (IC50 values in the low picomolar range). A more thorough characterization of the roles of endocannabinoids in health and disease will be necessary to define the significance of endocannabinoid inactivation mechanisms as targets for therapeutic drugs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-arachidonylglycerol, http://linkedlifedata.com/resource/pubmed/chemical/Amidohydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Cannabinoids, http://linkedlifedata.com/resource/pubmed/chemical/Endocannabinoids, http://linkedlifedata.com/resource/pubmed/chemical/Glycerides, http://linkedlifedata.com/resource/pubmed/chemical/N-(4-hydroxyphenyl)arachidonylamide, http://linkedlifedata.com/resource/pubmed/chemical/Piperidines, http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cannabinoid, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug, http://linkedlifedata.com/resource/pubmed/chemical/anandamide amidohydrolase, http://linkedlifedata.com/resource/pubmed/chemical/rimonabant
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
298
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7-14
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Mechanisms of endocannabinoid inactivation: biochemistry and pharmacology.
pubmed:affiliation
Department of Pharmacology, University of California, Irvine, California 92697-4625, USA. agiuffri@uci.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review