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Thrombin‐stimulated proliferation is mediated by endothelin‐1 in cultured rat gingival fibroblasts
Author(s) -
Ohuchi Nozomi,
Hayashi Kazuhiko,
Iwamoto Keishi,
Koike Katsuo,
Kizawa Yasuo,
Nukaga Michiyoshi,
Kakegawa Tomohito,
Murakami Hajime
Publication year - 2010
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.1472-8206.2009.00786.x
Subject(s) - thrombin , agonist , endothelin 1 , microbiology and biotechnology , cycloheximide , endocrinology , medicine , chemistry , cell growth , antagonist , receptor , biology , biochemistry , protein biosynthesis , platelet
Endothelin‐1 (ET‐1) appears to be involved in drug‐induced proliferation of gingival fibroblasts. Thrombin induces proliferation of human gingival fibroblasts via protease‐activated receptor 1 (PAR1). In this study, using cultured rat gingival fibroblasts, we investigated whether thrombin‐induced proliferation of gingival fibroblasts is mediated by ET‐1. Thrombin‐induced proliferation (0.05–2.5 U/mL). Proliferation was also induced by a PAR1‐specific agonist (TFLLR‐NH 2, 0.1–30 μ m ), but not by a PAR2‐specific agonist (SLIGRL‐NH 2 ). Thrombin (2.5 U/mL) induced an increase in immunoreactive ET‐1 expression, which was inhibited by cycloheximide (10 μg/mL), and an increase in preproET‐1 mRNA expression, as assessed by reverse transcription polymerase chain reaction. TFLLR‐NH 2 increased ET‐1 release into the culture medium in both a concentration (0.01–10 μ m )‐ and time (6–24 h)‐dependent manner, as assessed by solid phase sandwich enzyme‐linked immunosorbent assay. The thrombin (2.5 U/mL)‐induced proliferation was inhibited by a PAR1‐selective inhibitor, SCH79797 (0.1 μ m ) and an ET A antagonist, BQ‐123 (1 μ m ), but not by an ET B antagonist, BQ‐788 (1 μ m ). These findings suggest that thrombin, acting via PAR1, induced proliferation of cultured rat gingival fibroblasts that was mediated by ET‐1 acting via ET A .