Dopamine receptors labelled by [3H]quinpirole.
Since quinpirole (or LY171555) has a high affinity for dopamine D2 receptors, and since the high-affinity state of D2 appears to be the functional state of D2, we prepared [3H]quinpirole to investigate its suitability for labelling the high-affinity state of the D2 receptor. The dissociation constant of [3H]quinpirole binding to canine striatum homogenate was 3.9 nM in the absence of NaCl and 6.8 nM in the presence of NaCl. Only 50% of the total binding was specifically displaced by 10 microM S-sulpiride. The data are consistent with the conclusion that much or most of the [3H]quinpirole binds to the high-affinity state of the D2 receptor, since dopamine D2 agonists and antagonists were the most potent in inhibiting the binding of this ligand, because the density of binding sites was 8-9 pmol/g, about half that for [3H]spiperone, and because the density was reduced by 70% in the presence of guanylylimidodiphosphate. Since quinpirole has a reported Ki value of 5.1 nM for dopamine D3 receptors, similar to the quinpirole Ki value of 4.8 nM for the high-affinity state of the dopamine D2 receptor, it appears that [3H]quinpirole with its Kd of 3.9-6.8 nM could label both these two dopamine receptors. However, since the spiperone and haloperidol Ki values against [3H]quinpirole were the same as their values at dopamine D2 receptors rather than dopamine D3 receptors, it appears that [3H]quinpirole predominantly labels dopamine D2 receptors in the canine striatum. The guanine nucleotide-insensitive component of [3H]quinpirole binding (about 30%) may be to dopamine D3 receptors.
Seeman
P
P
Department of Pharmacology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Schaus
J M
JM
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000494:pharmacology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D006150:Guanine Nucleotides; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D013134:Spiperone; D006220:Haloperidol