%0 Journal Article
%A Sihver, W.
%A Schulze, A.
%A Wutz, W.
%A Stüsgen, S.
%A Olsson, R. A.
%A Bier, D.
%A Holschbach, M. H.
%T Autoradiographic comparison of in vitro binding characteristics of various tritiated adenosine A2A receptor ligands in rat, mouse and pig brain and first ex vivo results
%J European journal of pharmacology / Environmental toxicology and pharmacology
%V 616
%@ 0926-6917
%C Amsterdam
%I Elsevier
%M PreJuSER-1695
%D 2009
%Z Record converted from VDB: 12.11.2012
%X 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.
%K Adenosine A2 Receptor Agonists
%K Animals
%K Autoradiography
%K Blood-Brain Barrier: metabolism
%K Brain: metabolism
%K Cell Membrane: metabolism
%K Chromatography, High Pressure Liquid
%K Female
%K Ligands
%K Mice
%K PC12 Cells
%K Protein Binding
%K Rats
%K Receptor, Adenosine A2A: metabolism
%K Swine
%K Tritium: chemistry
%K Xanthines: chemistry
%K Xanthines: metabolism
%K Adenosine A2 Receptor Agonists (NLM Chemicals)
%K Ligands (NLM Chemicals)
%K MSX 2 compound (NLM Chemicals)
%K Receptor, Adenosine A2A (NLM Chemicals)
%K Xanthines (NLM Chemicals)
%K Tritium (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:19545560
%U <Go to ISI:>//WOS:000269933100017
%R 10.1016/j.ejphar.2009.06.025
%U https://juser.fz-juelich.de/record/1695