Dopaminergic inhibition of DNA synthesis in pituitary tumor cells is associated with phosphotyrosine phosphatase activity

• Published in: The Journal of biological chemistry Vol. 267; no. 34; pp. 24169 - 24172
• Main Authors: FLORIO, T, MING-GUI PAN, NEWMAN, B, HERSHBERGER, R. E, CIVELLI, O, STORK, P. J. S
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 05.12.1992
• Subjects: Adenylyl Cyclases - metabolism; Animals; Biological and medical sciences; Biological Transport - drug effects; Cell physiology; DNA Replication - drug effects; DNA, Neoplasm - biosynthesis; Dopamine - pharmacology; Fundamental and applied biological sciences. Psychology; Haloperidol - pharmacology; Hormonal regulation; Humans; Kinetics; Molecular and cellular biology; Pertussis Toxin; Pituitary Neoplasms; Protein Tyrosine Phosphatases - metabolism; Rats; Receptors, Dopamine D1 - drug effects; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - physiology; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - physiology; Somatostatin - pharmacology; Thymidine - metabolism; Transfection; Tritium; Tumor Cells, Cultured; Vanadates - pharmacology; Virulence Factors, Bordetella - pharmacology; Vertebrata; Mammalia; Dopamine; D2 Dopamine receptor; Rat; Enzyme; Rodentia; Pituicyte; DNA synthesis; Inhibition; Tumor cell; Protein-tyrosine-phosphatase
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)35744-2

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.