3H]N-propylapomorphine and [3H]spiperone binding in brain indicate two states of the D2-dopamine receptor

[3H]N-propylapomorphine ([3H]NPA) a dopaminergic catecholamine derivative, labels a sub-set of D2-dopamine receptors in bovine caudate particulate preparation. [3H]Spiperone, a dopamine receptor antagonist, labels twice as many sites as [3H]NPA. Dopaminergic ergots and potent neuroleptics compete for both radioactive ligands with similar high affinities. Catecholamines and catecholamine derivatives compete more potently for [3H]NPA binding than for [3H]spiperone binding. Guanyl nucleotides reduce both [3H]NPA binding and the high affinity phase of catecholamine and catecholamine derivative competition for [3H]spiperone binding. These results are similar to binding results reported in studies of two-state receptors linked to adenylate cyclase such as the beta-adrenergic receptors. These observations indicate that the D2-dopamine receptor in the brain may exist in two states and may be inversely coupled to brain adenylate cyclase activity.