% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Sihver:1695, author = {Sihver, W. and Schulze, A. and Wutz, W. and Stüsgen, S. and Olsson, R. A. and Bier, D. and Holschbach, M. H.}, title = {{A}utoradiographic comparison of in vitro binding characteristics of various tritiated adenosine {A}2{A} receptor ligands in rat, mouse and pig brain and first ex vivo results}, journal = {European journal of pharmacology / Environmental toxicology and pharmacology}, volume = {616}, issn = {0926-6917}, address = {Amsterdam}, publisher = {Elsevier}, reportid = {PreJuSER-1695}, year = {2009}, note = {Record converted from VDB: 12.11.2012}, abstract = {The adenosine A(2A) receptor in the basal ganglia is involved in the control of movement and plays a role in movement disorders such as Parkinsonism. Developing ligands to evaluate that receptor by noninvasive methods such as positron emission tomography has a high priority. In vitro radioligand binding guides the selection of ligands for in vivo application. This study measured the binding of the adenosine A(2A) receptor antagonist [(3)H]MSX-2 (3-(3-hydroxypropyl)-8-m-methoxystyryl)-7-methyl-1-propargylxanthine) to rat, mouse and pig brain by autoradiography. Other studies measured binding to membranes from PC12 pheochromocytoma cells. Those binding parameters were compared to those of the adenosine A(2A) receptor antagonist [(3)H]ZM241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino)ethyl)phenol), the adenosine A(2A) receptor agonist [(3)H]CGS21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine) and the unselective adenosine receptor agonist [(3)H]NECA (5'N-ethylcarboxamido)adenosine). The potency order (K(d)) in the three species was [(3)H]ZM241385<[(3)H]MSX-2<[(3)H]NECA<[(3)H]CGS21680. The density of [(3)H]MSX-2 binding sites was greater in the striatum than in the cortex. Preliminary ex vivo experiments showed that by 10min after iv injection, [(3)H]MSX-2 and [(3)H]CGS21680 crossed the blood-brain barrier to the extent of almost $1\%$ ID/g brain tissue, but [(3)H]NECA and [(3)H]ZM241385 to only $0.2\%$ ID/g. The prior administration of unlabeled ZM241385 significantly lowered brain uptake of [(3)H]MSX-2. In conclusion, [(3)H]MSX-2 has a high affinity and sufficient selectivity for the adenosine A(2A) receptor. It penetrates the blood-brain barrier. Sensitivity to photoisomerization is a limitation. Further investigations assess its suitability as a ligand for imaging the brain adenosine A(2A) receptor.}, keywords = {Adenosine A2 Receptor Agonists / Animals / Autoradiography / Blood-Brain Barrier: metabolism / Brain: metabolism / Cell Membrane: metabolism / Chromatography, High Pressure Liquid / Female / Ligands / Mice / PC12 Cells / Protein Binding / Rats / Receptor, Adenosine A2A: metabolism / Swine / Tritium: chemistry / Xanthines: chemistry / Xanthines: metabolism / Adenosine A2 Receptor Agonists (NLM Chemicals) / Ligands (NLM Chemicals) / MSX 2 compound (NLM Chemicals) / Receptor, Adenosine A2A (NLM Chemicals) / Xanthines (NLM Chemicals) / Tritium (NLM Chemicals) / J (WoSType)}, cin = {INB-4}, ddc = {610}, cid = {I:(DE-Juel1)VDB807}, pnm = {Funktion und Dysfunktion des Nervensystems}, pid = {G:(DE-Juel1)FUEK409}, shelfmark = {Pharmacology $\&$ Pharmacy}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:19545560}, UT = {WOS:000269933100017}, doi = {10.1016/j.ejphar.2009.06.025}, url = {https://juser.fz-juelich.de/record/1695}, }