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rdf:type |
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lifeskim:mentions |
umls-concept:C0031715,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0039067,
umls-concept:C0114838,
umls-concept:C0127400,
umls-concept:C0206529,
umls-concept:C0521390,
umls-concept:C1152949,
umls-concept:C1333712,
umls-concept:C1522240,
umls-concept:C1709059
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pubmed:issue |
5
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pubmed:dateCreated |
2001-3-12
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pubmed:abstractText |
There is considerable evidence that the activity of the neuronal dopamine transporter (DAT) is dynamically regulated and a putative implication of its phosphorylation in this process has been proposed. However, there is little information available regarding the nature of physiological stimuli that contribute to the endogenous control of the DAT function. Based on the close relationship between glutamatergic and dopaminergic systems in the striatum, we investigated the modulation of the DAT activity by metabotropic glutamate receptors (mGluRs). Short-term incubations of rat striatal synaptosomes with micromolar concentrations of the group I mGluR selective agonist (S)-3,5-dihydroxyphenylglycine were found to significantly decrease the DAT capacity and efficiency. This alteration was completely prevented by a highly selective mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). The effect of (S)-3,5-dihydroxyphenylglycine was also inhibited by staurosporine and by selective inhibitors of protein kinase C and calcium calmodulin-dependent protein kinase II. Co-application of okadaic acid prolonged the transient effect of the agonist, supporting a critical role for phosphorylation in the modulation of the DAT activity by mGluRs. In conclusion, we propose that striatal mGluR5 contribute to the control of the DAT activity through concomitant activation of both protein kinase C and calcium calmodulin-dependent protein kinase II.
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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/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/3,5-dihydroxyphenylglycine,
http://linkedlifedata.com/resource/pubmed/chemical/6-methyl-2-(phenylethynyl)pyridine,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Plasma Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/KN 62,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/Resorcinols,
http://linkedlifedata.com/resource/pubmed/chemical/Ro 31-8220,
http://linkedlifedata.com/resource/pubmed/chemical/Slc6a3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/metabotropic glutamate receptor 5
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
76
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1282-90
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11238713-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:11238713-Animals,
pubmed-meshheading:11238713-Carrier Proteins,
pubmed-meshheading:11238713-Corpus Striatum,
pubmed-meshheading:11238713-Dopamine,
pubmed-meshheading:11238713-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:11238713-Enzyme Inhibitors,
pubmed-meshheading:11238713-Excitatory Amino Acid Antagonists,
pubmed-meshheading:11238713-Glycine,
pubmed-meshheading:11238713-Indoles,
pubmed-meshheading:11238713-Isoquinolines,
pubmed-meshheading:11238713-Kinetics,
pubmed-meshheading:11238713-Male,
pubmed-meshheading:11238713-Membrane Glycoproteins,
pubmed-meshheading:11238713-Membrane Transport Proteins,
pubmed-meshheading:11238713-Nerve Tissue Proteins,
pubmed-meshheading:11238713-Neurons,
pubmed-meshheading:11238713-Phosphorylation,
pubmed-meshheading:11238713-Pyridines,
pubmed-meshheading:11238713-Rats,
pubmed-meshheading:11238713-Rats, Wistar,
pubmed-meshheading:11238713-Receptors, Metabotropic Glutamate,
pubmed-meshheading:11238713-Resorcinols,
pubmed-meshheading:11238713-Staurosporine,
pubmed-meshheading:11238713-Sulfonamides,
pubmed-meshheading:11238713-Synaptosomes,
pubmed-meshheading:11238713-Tetradecanoylphorbol Acetate
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pubmed:year |
2001
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pubmed:articleTitle |
Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes.
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pubmed:affiliation |
Laboratoire de Pharmacologie Expérimentale (FARL), Université Catholique de Louvain 54.10, Brussels, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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