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| Home > Publications database > 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 |
| Home > Publications database > 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 |
| Journal Article | PreJuSER-1695 |
; ; ; ; ; ;
2009
Elsevier
Amsterdam
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Please use a persistent id in citations: doi:10.1016/j.ejphar.2009.06.025
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.
Keyword(s): Adenosine A2 Receptor Agonists (MeSH) ; Animals (MeSH) ; Autoradiography (MeSH) ; Blood-Brain Barrier: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Cell Membrane: metabolism (MeSH) ; Chromatography, High Pressure Liquid (MeSH) ; Female (MeSH) ; Ligands (MeSH) ; Mice (MeSH) ; PC12 Cells (MeSH) ; Protein Binding (MeSH) ; Rats (MeSH) ; Receptor, Adenosine A2A: metabolism (MeSH) ; Swine (MeSH) ; Tritium: chemistry (MeSH) ; Xanthines: chemistry (MeSH) ; Xanthines: metabolism (MeSH) ; Adenosine A2 Receptor Agonists ; Ligands ; MSX 2 compound ; Receptor, Adenosine A2A ; Xanthines ; Tritium ; J ; Adenosine A(2A) receptor (auto) ; [H-3]ZM241385 (auto) ; [H-3]CGS21680 (auto) ; [H-3]MSX-2 (auto) ; [H-3]NECA (auto) ; Brain imaging (auto)
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