Inhibition of angiotensin II- and endothelin-1-stimulated proliferation by selective MEK inhibitor in cultured rabbit gingival fibroblastsdagger.
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.
Ohsawa
Masami
M
Division of Health and Sport Sciences, Nihon University College of Industrial Technology, Mimomi Campus, Shinsakae, Narashino, Chiba 274-8576, Japan.
Ohuchi
Nozomi
N
Taniguchi
Yumiko
Y
Kizawa
Yasuo
Y
Koike
Katsuo
K
Iwamoto
Keishi
K
Hayashi
Kazuhiko
K
Murakami
Hajime
H
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D012504:Saralasin / Q000494:pharmacology
D002070:Butadienes; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009570:Nitriles; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C113580:U 0126; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D012504:Saralasin; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one