TY  - JOUR
AU  - Sihver, W.
AU  - Schulze, A.
AU  - Wutz, W.
AU  - Stüsgen, S.
AU  - Olsson, R. A.
AU  - Bier, D.
AU  - Holschbach, M. H.
TI  - 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
JO  - European journal of pharmacology / Environmental toxicology and pharmacology
VL  - 616
SN  - 0926-6917
CY  - Amsterdam
PB  - Elsevier
M1  - PreJuSER-1695
PY  - 2009
N1  - Record converted from VDB: 12.11.2012
AB  - 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.
KW  - Adenosine A2 Receptor Agonists
KW  - Animals
KW  - Autoradiography
KW  - Blood-Brain Barrier: metabolism
KW  - Brain: metabolism
KW  - Cell Membrane: metabolism
KW  - Chromatography, High Pressure Liquid
KW  - Female
KW  - Ligands
KW  - Mice
KW  - PC12 Cells
KW  - Protein Binding
KW  - Rats
KW  - Receptor, Adenosine A2A: metabolism
KW  - Swine
KW  - Tritium: chemistry
KW  - Xanthines: chemistry
KW  - Xanthines: metabolism
KW  - Adenosine A2 Receptor Agonists (NLM Chemicals)
KW  - Ligands (NLM Chemicals)
KW  - MSX 2 compound (NLM Chemicals)
KW  - Receptor, Adenosine A2A (NLM Chemicals)
KW  - Xanthines (NLM Chemicals)
KW  - Tritium (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:19545560
UR  - <Go to ISI:>//WOS:000269933100017
DO  - DOI:10.1016/j.ejphar.2009.06.025
UR  - https://juser.fz-juelich.de/record/1695
ER  -