We have investigated the structure of
dopamine (DA) D2 receptors present in an
estrone-induced,
prolactin (PRL)-secreting, DA-sensitive
adenoma and in two PRL-secreting and DA-insensitive transplantable
tumors 7315a and MtTW15, in order to identify better the anomalies present in DA-resistant lactotrophs. D2 receptors were found in both a high- and a low-affinity state in adenomatous lactotrophs as shown by displacement studies with the agonist
N-propylnorapomorphine (NPA), but only in the low-affinity state in the two DA-resistant
tumors. Treatment with the
alkylating agent N-ethylmaleimide induced a disappearance of the high-affinity state of the D2 receptor in the
adenoma and a reduction in receptor concentration, but did not have any effect on the affinity of receptors present in DA-resistant
tumors. Moreover, target size analysis and radiation inactivation studies of D2 receptors, using membranes preincubated with NPA and [3H]
spiperone as
ligand or using [3H]NPA as
ligand on membranes preparations, have shown the presence of distinct structural differences between adenomatous and tumoral D2 receptors and between the two tumoral receptors themselves; these results suggest that the normal functional unit of the D2 receptor is a dimer associated with a
guanine nucleotide-
binding protein (
G protein) subunit and that tumoral D2 receptors may exist in various polymeric forms unassociated with
G proteins. The anomalies found to be present in tumoral D2 receptor complexes may be responsible for the insensitivity of these
tumors to
dopaminergic agonists' inhibitory activity on PRL release and
tumor growth.