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Structural Differences Between Dopamine D 2 Receptors Present in a Rat Pituitary Adenoma and in Transplantable Rat Pituitary Tumors 7315a and MtTW15
Author(s) -
Bouvier C.,
Lagacé G.,
Potier M.,
Collu R.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb02324.x
Subject(s) - receptor , dopamine receptor , dopaminergic , endocrinology , medicine , agonist , chemistry , adenoma , g protein , dopamine , biology , biochemistry
We have investigated the structure of dopamine (DA) D 2 receptors present in an estrone‐induced, prolactin (PRL)‐secreting, DA‐sensitive adenoma and in two PRL‐secreting and DA‐insensitive transplantable tumors 7315, and MtTW15, in order to identify better the anomalies present in DA‐resistant lactotrophs. D 2 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 D 2 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 D 2 receptors, using membranes preincubated with NPA and [ 3 H]spiperone as ligand or using [ 3 H]NPA as ligand on membranes preparations, have shown the presence of distinct structural differences between adenomatous and tumoral D 2 receptors and between the two tumoral receptors themselves; these results suggest that the normal functional unit of the D 2 receptor is a dimer associated with a guanine nucleotide‐binding protein (G protein) subunit and that tumoral D 2 receptors may exist in various polymeric forms unassociated with G proteins. The anomalies found to be present in tumoral D 2 receptor complexes may be responsible for the insensitivity of these tumors to dopaminergic agonists’inhibitory activity on PRL release and tumor growth.