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Inhibition of angiotensin II‐ and endothelin‐1‐stimulated proliferation by selective MEK inhibitor in cultured rabbit gingival fibroblasts †
Author(s) -
Ohsawa Masami,
Ohuchi Nozomi,
Taniguchi Yumiko,
Kizawa Yasuo,
Koike Katsuo,
Iwamoto Keishi,
Hayashi Kazuhiko,
Murakami Hajime
Publication year - 2005
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2005.00372.x
Subject(s) - endothelin 1 , rabbit (cipher) , angiotensin ii , renin–angiotensin system , endothelin receptor , chemistry , endocrinology , medicine , pharmacology , biology , receptor , blood pressure , statistics , mathematics
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 AT 1 antagonist, and saralasin, an AT 1 /AT 2 antagonist, but not by PD123,319, an AT 2 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 ET A 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 ET A inhibitor, and TAK044, an ET A /ET B inhibitor, but not by BQ‐788, an ET B 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, AT 1 and ET A in CRGF.