Binding of [3H]PD 128907, a putatively selective ligand for the D3 dopamine receptor, in rat brain: a receptor binding and quantitative autoradiographic study.
[3H]PD 128907 has been proposed as a selective ligand for the D3 dopamine receptor. This study characterizes the binding of this radioligand in rat brain using in vitro radioligand binding and autoradiographic methods. In radioligand binding studies, [3H]PD 128907 exhibited 0.3 nmol/L affinity for a single, low density site in ventral striatal membranes. The pharmacological profile for [3H]PD 128907 was similar to that of [3H](+)-7-OH-DPAT with the rank order of potency for dopamine agonists being PD 128907 approximately 7-OH-DPAT approximately quinpirole > or = dopamine; for antagonists, spiperone > (+)-butaclamol approximately domperidone > or = haloperidol > SCH 23390. Guanyl nucleotides had no effect on the binding of either ligand. These observations indicate labeling of a dopaminergic site with characteristics consistent with the D3 receptor. In autoradiographic studies, highest densities of [3H]PD 128907-labeled sites were observed in islands of Calleja followed by the nucleus accumbens, nucleus of the horizontal limb of the diagonal band, the molecular layer of cerebellar lobule X, and the ventral caudate/putamen.
Bancroft
G N
GN
Department of Pharmacology, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Morgan
K A
KA
Flietstra
R J
RJ
Levant
B
B
D000818:Animals; D001345:Autoradiography; D001578:Benzopyrans / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D018491:Dopamine Agonists / Q000493:pharmacokinetics*; D006150:Guanine Nucleotides / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D010078:Oxazines / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000096:biosynthesis; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D001578:Benzopyrans; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D006150:Guanine Nucleotides; D008024:Ligands; D010078:Oxazines; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; C031349:7-hydroxy-2-N,N-dipropylaminotetralin