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1 June 2000 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
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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.

Haruhiko Kanasaki, Kohji Fukunaga, Kentaro Takahashi, Kohji Miyazaki, and Eishichi Miyamoto "Involvement of p38 Mitogen-Activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 Cells," Biology of Reproduction 62(6), 1486-1494, (1 June 2000). https://doi.org/10.1095/biolreprod62.6.1486
Received: 3 August 1999; Accepted: 1 December 1999; Published: 1 June 2000
JOURNAL ARTICLE
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