Dopamine D2 receptors selectively labeled by a benzamide neuroleptic: [3H]-YM-09151-2 |
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Authors: | H B Niznik D E Grigoriadis I Pri-Bar O Buchman P Seeman |
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Institution: | (1) Department of Pharmacology, Faculty of Medicine, University of Toronto, M5S 1A8 Toronto, Ontario, Canada;(2) Radiochemistry Department, Nuclear Research Center, Negev, P.O. Box 9001, Beer-Sheva, Israel |
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Abstract: | Summary In order to label dopamine D2 receptors selectively we tritiated the potent benzamide neuroleptic, YM-09151-2 (26.7 Ci/mmol). The binding of 3H]-YM-09151-2 to canine striatal membranes was saturable and specific with a K
D of 57 pmol/l and B
max of 36 pmol/g tissue as determined by Scatchard analysis. The K
D, but not the B
max, of 3H]-YM-09151-2 increased 6-fold in the absence of sodium chloride. 3H]-YM-09151-2 labeled 40% more sites than 3H]-spiperone in the same tissue homogenate. 3H]-YM-09151-2 binding was inhibited by dopaminergic drugs in a concentration and stereoselective manner with the appropriate dopamine D2 receptor profile. Thus, dopamine agonists inhibited 3H]-YM-09151-2 binding to canine striatal membranes with the following rank order of potency: (–)-N-n-propylnorapomorphine > apomorphine > (±)-6,7-dihydroxy-2-aminotetralin > (+)-N-n-propylnorapomorphine > dopamine > (–)-noradrenaline > serotonin > (–)-isoprenaline. Dopaminergic antagonists competed for 3H]-YM-09151-2 binding with the following order of potency: spiperone > (+)-butaclamol > haloperidol > clebopride > (–)-sulpiride > SCH-23390 > (–)-butaclamol. Furthermore, dopamine agonists recognized 2 states of the receptor labeled by 3H]-YM-09151-2, D
2
high
and D
2
low
. The D
2
high
state of the receptor could be converted to D
2
low
by guanine nucleotides and sodium ions as is the case for 3H]-spiperone binding to D2 receptors. 3H]-YM-09151-2 appears to be a more selective ligand for dopamine D2 receptors than 3H]-spiperone, since YM-09151-2 displays approximately 9-fold lower affinity than spiperone for cortical serotonergic (S2) receptors. 3H]-YM-09151-2 may become a useful tool for the selective characterization of dopamine D2 receptors.Abbreviations used (±)ADTN
(±)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene
- NPA
N-n-propylnorapomorphine
- Gpp(NH)p
5 -guanylylimidodiphosphate |
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Keywords: | Dopamine D2 receptors Benzamide neuroleptics [3H]-YM-09151-2 [3H]-Spiperone Labeling |
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