Regulation and molecular characterization of dopamine D2 receptors in a prolactin-secreting 7315a anterior pituitary tumor.
The regulation and molecular properties of the dopamine (DA) D2 receptors were compared in the prolactin-secreting 7315a anterior pituitary tumor with those in the striatum of rats. Chronic treatment with haloperidol increases the maximal binding for [3H]spiroperidol in tumor and striatum, but the percent increase is much higher in tumor than in striatum. Photoaffinity labelling of DA D2 receptors with N-(p-azido-m-[125I]iodophenethyl)spiperone ([125I]N3-NAPS) yielded a major specifically labeled peptide with the Mr of 32-34 kDa in tumor, and two specifically labeled peptides with Mr of 32-34 and 92-94 kDa in striatum. The analysis of DA D2 receptor mRNA shows that the size is similar in tumor and striatum. The DA D2 receptor mRNA in tumor is very low and chronic treatment with haloperidol produces a considerable increase of the specific mRNA. It is postulated that the reported defect in regulation of prolactin release by DA agonists might be due to posttranslational changes in the tumor DA D2 receptor.
Department of Psychiatry, New York University Medical Center, NY 10016.
J Y
JY
Lew
H
H
Zawadzka
D
D
Feigenblum
D
D
Tang
D
D
Filer
P
P
Benedetto
M
M
Goldstein
D000818:Animals; D001386:Azides; D015152:Blotting, Northern; D002069:Butaclamol / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009374:Neoplasms, Experimental / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF; D011954:Receptors, Dopamine / Q000032:analysis / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives
D001386:Azides; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D013134:Spiperone; D011388:Prolactin; C044567:N-(4-azido-3-iodophenethyl)spiperone; D002069:Butaclamol; D006220:Haloperidol