Single apomorphine pretreatment results in a rapid decline in high-affinity dopamine binding to the striatal dopamine D-2 receptor.
The formation of a ternary complex of agonist, receptor, and G-protein precedes inhibition of adenylate cyclase and is associated with high-affinity agonist binding. The present experiment was conducted to determine if a single direct dopamine (DA) agonist, apomorphine (APO), pretreatment could produce a rapid uncoupling of the striatal DA D-2 receptor from its G-proteins. APO (30 mg/kg, i.p.) and saline were administered once, with killing 60 or 90 min following the APO or vehicle treatment. APO pretreatment resulted in a reduction in the high-affinity binding of DA to the striatal DA D-2 receptor without altering total agonist binding. The total density of antagonist-defined D-2 receptors (Bmax) was not altered by the treatment. The present results represent, to our knowledge, the first demonstration of changes in high-affinity agonist binding to the DA D-2 receptor following a single in vivo pretreatment of a direct DA agonist.
Severson
J A
JA
Department of Psychiatry, School of Medicine, University of Southern California, Los Angeles 90033.
Randall
P K
PK
Wilcox
R E
RE
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism
D011954:Receptors, Dopamine; D013134:Spiperone; D019204:GTP-Binding Proteins; D001058:Apomorphine; D004298:Dopamine