3H]N-propylapomorphine and [ 3H]spiperone binding in brain indicate two states of the D 2-dopamine receptor

Abstract

[ 3H]N-propylapomorphine ([ 3H]NPA) a dopaminergic catecholamine derivative, labels a sub-set of D 2-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 β-adrenergic receptors. These observations indicate that the D 2-dopamine receptor in the brain may exist in two states and may be inversely coupled to brain adenylate cyclase activity.