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Characterization of D 2 Dopamine Receptors in Dopamine‐Resistant Prolactin‐Secreting Rat Pituitary Tumors 7315a and MtTW15
Author(s) -
Bouvier C.,
Lagacé G.,
Lafond J.,
Beauregard G.,
Potier M.,
Collu R.
Publication year - 1987
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.1471-4159.1987.tb01038.x
Subject(s) - chemistry , receptor , dopamine receptor , agonist , dopamine , spiperone , photoaffinity labeling , biochemistry , sodium dodecyl sulfate , endocrinology , biology
We have investigated the structure of D 2 receptors present in two prolactin‐secreting, dopamine‐resistant, transplantable rat pituitary tumors, 7315a and MtTWIS. These receptors specifically bind with high affinity the do‐pamine antagonist [ 3 H]spiroperidol when membrane bound or solubilized by [3‐(3‐cholamidopropyl)‐dimethyl‐ammonio]‐1‐propane sulfonate 10 m M and are pharmacologically characterized as D 2 type. Target‐size analysis by radiation inactivation indicated a molecular mass of approximately 100,000 and 200,000 daltons for receptors present respectively in 7315a and MtTWIS tumors either membrane bound or solubilized. The minimal size of the D 2 binding site was evaluated at 94,000 daltons by photoaffinity labeling with [ 125 I]azido‐ N ‐( p ‐aminophenethyl)‐spiperone followed by sodium dodecyl sulfate‐polyacryl‐amide gel electrophoresis. A guanine nucleotide had no effect on the displacing potency of the agonist N ‐propyl‐norapomorphine evaluated with membrane‐bound or solubilized receptors obtained from either tumor. These results suggest the absence or inactivation of a guanine nucleotide binding protein in the receptorial complex of these tumors. Thus, our data indicate that a structural anomaly is present in the D 2 receptorial complex of these prolactin‐secreting rat pituitary tumors, which may be responsible for their resistance to the inhibitory effects of dopamine.