Inhibition of angiotensin II- and endothelin-1-stimulated proliferation by selective MEK inhibitor in cultured rabbit gingival fibroblasts.

Autor: Ohsawa, Masami, Ohuchi, Nozomi, Taniguchi, Yumiko, Kizawa, Yasuo, Koike, Katsuo, Iwamoto, Keishi, Hayashi, Kazuhiko, Murakami, Hajime
Předmět:
Zdroj: Fundamental & Clinical Pharmacology; Dec2005, Vol. 19 Issue 6, p677-685, 9p
Abstrakt: We investigated the implication of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in the proliferation stimulated by angiotensin II (Ang II) and endothelin-1 (ET-1) in cultured rabbit gingival fibroblasts (CRGF). Ang II stimulated activation of ERK1/2 and the activation was inhibited by CV-11974, an AT1 antagonist, and saralasin, an AT1/AT2 antagonist, but not by PD123,319, an AT2 antagonist in the CRGF. Ang II-stimulated proliferation was inhibited by PD98059 or U0126, selective MEK inhibitors. Furthermore, ET-1 stimulated proliferation via G-protein-coupled ETA receptors, which were identified by Western blot analysis of membrane protein from the CRGF. ET-1 also stimulated activation of ERK1/2 and the activation was inhibited by BQ-123, an ETA inhibitor, and TAK044, an ETA/ETB inhibitor, but not by BQ-788, an ETB inhibitor. ET-1-stimulated proliferation was inhibited by PD98059 or U0126. These findings suggest that ERK1/2 play a role in the signaling process leading to proliferation stimulated by Ang II and ET-1 via G-protein-coupled receptors, AT1 and ETA in CRGF. [ABSTRACT FROM AUTHOR]
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