Dopamine D2 receptor binding in adrenal medulla: Characterization using [3H]spiperone

Abstract The possibility that dopamine may function as a neuromodulator or neurotransmitter in the adrenal gland, and not merely serve as a precursor to the catecholamines, has been suggested. If this hypothesis is correct, receptors for dopamine should be identifiable in the adrenal. The present work demonstrates the existence of a high-affinity receptor in adrenal medulla using [ 3 H]spiperone as the radioligand to label the receptors. [ 3 H]Spiperone bound rapidly, reversibly, and with high affinity to bovine adrenal medullary membranes. Scatchard analysis yielded a K d of 0.09 nM and a B max of 51 fmol/ mg protein. In competition binding experiments, dopaminergic antagonists were at least 100 times more potent in displacing [ 3 H]spiperone from its binding sites than adrenergic or serotonergic receptor antagonists. Similarly, agonists at the dopamine receptor more readily competed for [ 3 H]spiperone binding than other receptor agonist drugs tested. Furthermore, D2 selective antagonists and agonists were much more potent than D1 receptor ligands. These results suggest that [ 3 H]spiperone may bind to a high-affinity D2 dopamine receptor in adrenal medulla.