DOPAMINE-RECEPTORS LABELED BY [H-3] 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 [H-3]quinpirole to investigate its suitability for labelling the high-affinity state of the D2 receptor. The dissociation constant of [H-3]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-mu-M S-sulpiride. The data are consistent with the conclusion that much or most of the [H-3]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 [H-3]spiperone, and because the density was reduced by 70% in the presence of guanylylimidodiphosphate. Since quinpirole has a reported K(i) value of 5.1 nM for dopamine D3 receptors, similar to the quinpirole K(i) value of 4.8 nM for the high-affinity state of the dopamine D2 receptor, it appears that [H-3]quinpirole with its K(d) of 3.9-6.8 nM could label both these two dopamine receptors. However, since the spiperone and haloperidol K(i) values against [H-3]quinpirole were the same as their values at dopamine D2 receptors rather than dopamine D3 receptors, it appears that [H-3]quinpirole predominantly labels dopamine D2 receptors in the canine striatum. The guanine nucleotide-insensitive component of [H-3]quinpirole binding (about 30%) may be to dopamine D3 receptors.