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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2002-8-14
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pubmed:abstractText |
Cannabinoid receptors and their endogenous ligands have been recently identified in the brain as potent inhibitors of neurotransmitter release. Here we show that, in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine (6-OHDA), the striatal levels of anandamide, but not that of the other endocannabinoid 2-arachidonoylglycerol, were increased. Moreover, we observed a decreased activity of the anandamide membrane transporter (AMT) and of the anandamide hydrolase [fatty acid amide hydrolase (FAAH)], whereas the binding of anandamide to cannabinoid receptors was unaffected. Spontaneous glutamatergic activity recorded from striatal spiny neurons was higher in 6-OHDA-lesioned rats. Inhibition of AMT by N-(4-hydroxyphenyl)-arachidonoylamide (AM-404) or by VDM11, or stimulation of the cannabinoid CB1 receptor by HU-210 reduced glutamatergic spontaneous activity in both naive and 6-OHDA-lesioned animals to a similar extent. Conversely, the FAAH inhibitors phenylmethylsulfonyl fluoride and methyl-arachidonoyl fluorophosphonate were much more effective in 6-OHDA-lesioned animals. The present study shows that inhibition of anandamide hydrolysis might represent a possible target to decrease the abnormal cortical glutamatergic drive in Parkinson's disease.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-arachidonylglycerol,
http://linkedlifedata.com/resource/pubmed/chemical/Amidohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Cannabinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endocannabinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerides,
http://linkedlifedata.com/resource/pubmed/chemical/HU 211,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-methyl-3-hydroxyphenyl)-5,8,11...,
http://linkedlifedata.com/resource/pubmed/chemical/N-(4-hydroxyphenyl)arachidonylamide,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Polyunsaturated Alkamides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cannabinoid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydrocannabinol,
http://linkedlifedata.com/resource/pubmed/chemical/anandamide,
http://linkedlifedata.com/resource/pubmed/chemical/fatty-acid amide hydrolase
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6900-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12177188-Amidohydrolases,
pubmed-meshheading:12177188-Animals,
pubmed-meshheading:12177188-Arachidonic Acids,
pubmed-meshheading:12177188-Cannabinoids,
pubmed-meshheading:12177188-Carrier Proteins,
pubmed-meshheading:12177188-Corpus Striatum,
pubmed-meshheading:12177188-Disease Models, Animal,
pubmed-meshheading:12177188-Endocannabinoids,
pubmed-meshheading:12177188-Enzyme Inhibitors,
pubmed-meshheading:12177188-Glutamic Acid,
pubmed-meshheading:12177188-Glycerides,
pubmed-meshheading:12177188-Hydrolysis,
pubmed-meshheading:12177188-Membrane Potentials,
pubmed-meshheading:12177188-Neurons,
pubmed-meshheading:12177188-Oxidopamine,
pubmed-meshheading:12177188-Parkinsonian Disorders,
pubmed-meshheading:12177188-Patch-Clamp Techniques,
pubmed-meshheading:12177188-Polyunsaturated Alkamides,
pubmed-meshheading:12177188-Rats,
pubmed-meshheading:12177188-Rats, Wistar,
pubmed-meshheading:12177188-Receptors, Cannabinoid,
pubmed-meshheading:12177188-Receptors, Drug,
pubmed-meshheading:12177188-Synaptic Transmission,
pubmed-meshheading:12177188-Tetrahydrocannabinol
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pubmed:year |
2002
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pubmed:articleTitle |
Experimental parkinsonism alters endocannabinoid degradation: implications for striatal glutamatergic transmission.
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pubmed:affiliation |
Dipartimentos di Neuroscienze, Università degli Studi di Roma Tor Vergata, 00133 Roma, Italy. paolo.calabresi@uniroma2.it
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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