The D2 dopamine receptor mediates inhibition of growth in GH4ZR7 cells

Involvement of protein kinase-C∈

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The D2 dopamine agonist, bromocriptine, has been used as treatment for human PRL-secreting pituitary adenomas. The result of bromocriptine treatment is often a substantial reduction of tumor mass, suggesting that the dopamine agonist is acting as an antiproliferative agent. This action can be observed with a clonal pituitary tumor cell line. The agonist activation of the D2 dopamine receptor inhibits the growth of GH4ZR7 cells, a GH4C1 cell line stably transfected with the cDNA encoding the short form of the D2 dopamine receptor. This effect of dopamine was not sensitive to overnight treatment with 100 ng/ml pertussis toxin. Treatment of GH4ZR7 cells with the phorbol ester 4 β-phorbol 12, 13-didecanoate resulted in the loss of dopaminergic inhibition of growth, whereas treatment with 4 α-phorbol 12, 13-didecanoate had no effect. Inhibitors of protein kinase-C (PKC), such as staurosporine and H7, also blocked the effect of dopamine. Down-regulation of cellular PKC by phorbol ester treatment resulted in a complete loss of dopaminergic inhibition of growth. Long term treatment of GH4ZR7 cells with TRH results in a specific down-regulation of the ∈ form of PKC and abolished the ability of dopamine to inhibit growth. These results suggest that PKC ∈ is involved in mediating the antiproliferative effects of dopamine. This mediation of growth appears to be through a novel signaling pathway for the D2 dopamine receptor.

Original languageEnglish (US)
Pages (from-to)783-789
Number of pages7
JournalEndocrinology
Volume134
Issue number2
DOIs
StatePublished - Jan 1 1994

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Dopamine D2 Receptors
Protein Kinase C
Dopamine
Growth
Bromocriptine
Dopamine Agonists
Phorbol Esters
Down-Regulation
Prolactinoma
Staurosporine
Pertussis Toxin
Pituitary Neoplasms
Tumor Cell Line
Complementary DNA
Cell Line
Neoplasms

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

The D2 dopamine receptor mediates inhibition of growth in GH4ZR7 cells : Involvement of protein kinase-C∈. / Senogles, Susan.

In: Endocrinology, Vol. 134, No. 2, 01.01.1994, p. 783-789.

Research output: Contribution to journalArticle

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