| pubmed-article:19217026 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19217026 | lifeskim:mentions | umls-concept:C0034798 | lld:lifeskim |
| pubmed-article:19217026 | lifeskim:mentions | umls-concept:C1704675 | lld:lifeskim |
| pubmed-article:19217026 | lifeskim:mentions | umls-concept:C0205464 | lld:lifeskim |
| pubmed-article:19217026 | lifeskim:mentions | umls-concept:C1880022 | lld:lifeskim |
| pubmed-article:19217026 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:19217026 | pubmed:dateCreated | 2009-4-8 | lld:pubmed |
| pubmed-article:19217026 | pubmed:abstractText | Dopaminergic signaling pathways have been extensively investigated using PET imaging, primarily with antagonist radioligands of D(2) and D(3) dopamine receptors (DARs). Recently, agonist radioligands of D(2)/D(3) DARs have begun to be developed and employed. One such agonist is (R)-2-(11)CH(3)O-N-n-propylnorapomorphine (MNPA). Here, we perform a pharmacological characterization of MNPA using recombinant D(2) and D(3) DARs expressed in HEK293 cells. MNPA was found to robustly inhibit forskolin-stimulated cAMP accumulation to the same extent as dopamine in D(2) or D(3) DAR-transfected cells, indicating that it is a full agonist at both receptors. MNPA is approximately 50-fold more potent than dopamine at the D(2) DAR, but equally potent as dopamine at the D(3) DAR. MNPA competition binding curves in membrane preparations expressing D(2) DARs revealed two binding states of high and low-affinity. In the presence of GTP, only one binding state of low affinity was observed. Direct saturation binding assays using [(3)H]MNPA revealed similar results as with the competition experiments leading to the conclusion that MNPA binds to the D(2) DAR in an agonist-specific fashion. In contrast to membrane preparations, using intact cell binding assays, only one site of low affinity was observed for MNPA and other agonists binding to the D(2) DAR. MNPA was also found to induce D(2) DAR internalization to an even greater extent than dopamine as determined using both cell surface receptor binding assays and confocal fluorescence microscopy. Taken together, our data indicate that the PET tracer, MNPA, is a full and potent agonist at both D(2) and D(3) receptors. | lld:pubmed |
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| pubmed-article:19217026 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19217026 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19217026 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19217026 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19217026 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19217026 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19217026 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:19217026 | pubmed:issn | 1098-2396 | lld:pubmed |
| pubmed-article:19217026 | pubmed:author | pubmed-author:HalldinChrist... | lld:pubmed |
| pubmed-article:19217026 | pubmed:author | pubmed-author:InnisRobert... | lld:pubmed |
| pubmed-article:19217026 | pubmed:author | pubmed-author:NamkungYoonY | lld:pubmed |
| pubmed-article:19217026 | pubmed:author | pubmed-author:SibleyDavid... | lld:pubmed |
| pubmed-article:19217026 | pubmed:author | pubmed-author:SkinbjergMett... | lld:pubmed |
| pubmed-article:19217026 | pubmed:copyrightInfo | Copyright 2009 Wiley-Liss, Inc. | lld:pubmed |
| pubmed-article:19217026 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19217026 | pubmed:volume | 63 | lld:pubmed |
| pubmed-article:19217026 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19217026 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19217026 | pubmed:pagination | 462-75 | lld:pubmed |
| pubmed-article:19217026 | pubmed:dateRevised | 2010-9-23 | lld:pubmed |
| pubmed-article:19217026 | pubmed:meshHeading | pubmed-meshheading:19217026... | lld:pubmed |
| pubmed-article:19217026 | pubmed:meshHeading | pubmed-meshheading:19217026... | lld:pubmed |
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