Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells

Haruhiko Kanasaki, Kohji Fukunaga, Kentaro Takahashi, Kohji Miyazaki, Eishichi Miyamoto

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Bromocriptine, a dopamine D2 receptor agonist, is a therapeutic agent for patients with prolactinoma and hyperprolactinemia. In this study we demonstrated that bromocriptine induced activation of p38 mitogen-activated protein (MAP) kinase, with concomitant induction of apoptosis in rat pituitary adenoma cell line GH3 cells. Treatment of GH3 cells for 48 h with bromocriptine increased the p38 MAP kinase activity up to 3- to 5-fold and simultaneously increased the number of apoptotic cells. Inclusion in the medium of SB212090 or SB203580, specific p38 MAP kinase inhibitors, completely abolished the bromocriptine-induced activation of p38 MAP kinase and significantly reduced the number of apoptotic cells. The bromocriptine- induced p38 MAP kinase activation was not prevented by S(-)-eticropride hydrochloride, a specific D2 receptor antagonist. Treatment with either epidermal growth factor (EGF) or thyrotropin-releasing hormone (TRH), which stimulates p44/42 MAP kinase, rescued cells from the bromocriptine-induced apoptosis, with concomitant inhibition of the bromocriptine-induced p38 MAP kinase activation. These results suggest that bromocriptine induces apoptosis in association with p38 MAP kinase activation, and that the p44/42 MAP kinase signaling through EGF and TRH receptors has an opposing effect on p38 MAP kinase activation as well as on apoptosis induced with bromocriptine in GH3 cells.

Original languageEnglish
Pages (from-to)1486-1494
Number of pages9
JournalBiology of Reproduction
Volume62
Issue number6
DOIs
Publication statusPublished - 2000 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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