Dopaminergic inhibition of DNA synthesis in pituitary tumor cells is associated with phosphotyrosine phosphatase activity.
Dopaminergic D2 receptor agonists, such as bromocriptine, are potent anti-proliferative agents in the treatment of human pituitary adenomas. We have reproduced the anti-proliferative effect of dopamine in an established pituitary cell line stably transfected with the rat D2 dopamine receptor cDNA. We found that dopaminergic inhibition of DNA synthesis parallels the stimulation of a phosphotyrosine phosphatase activity. Both actions are blocked by pertussis toxin and by the phosphotyrosine phosphatase inhibitor, vanadate. We suggest that the anti-proliferative action of dopamine is mediated, at least in part, by the dopaminergic stimulation of a phosphotyrosine phosphatase.
Florio
T
T
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201-3098.
Pan
M G
MG
Newman
B
B
Hershberger
R E
RE
Civelli
O
O
Stork
P J
PJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004298:Dopamine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D037342:Pertussis Toxin; D010911:Pituitary Neoplasms; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014316:Tritium; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D004273:DNA, Neoplasm; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D014316:Tritium; D014638:Vanadates; D013004:Somatostatin; D037342:Pertussis Toxin; D017027:Protein Tyrosine Phosphatases; D000262:Adenylyl Cyclases; D006220:Haloperidol; D013936:Thymidine; D004298:Dopamine