Cell-proliferative action of endothelin-1 in cultured bronchial smooth muscle cells of guinea pig

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.2), p.257-257
• Main Authors: Kizawa, Yasuo, Ohuchi, Nozomi, Saito, Kiyoshige, Kusama, Tadashi, Sano, Masakazu, Iwamoto, Keishi, Murakami, Hajime
• Format: Article
• Language: eng ; jpn
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)48492-8

Endothelin-1 (ET-1) is known to be a potent vascular and bronchial constrictor. It has also been reported that ET-1 acts as a co-mitogen with epidermal growth factor (EGF) in cultured human airway smooth muscle cells. This suggests that ET-1 may play a role in mediating airway smooth muscle proliferation, thereby contributing to airway remodelling. In this study, we investigated the proliferative effects of ET-1, both alone and in combination with EGF, in cultured bronchial smooth muscle cells of guinea pig. ET-1 (30- 100 nM) alone augmented cell proliferation, and also potentiated the effect of EGF (0.48 nM) in a concentration-dependent manner. An ET_A antagonist, BQ-123 (10 μM), reduced the cell-proliferative effect of ET-1, whereas an ET_B antagonist, BQ-788 (1 μM), did not influence the effect. Furthermore, the cell-proliferative action of ET-1 was partly reduced by a nitric oxide (NO) donor, SIN-1. These results suggest that ET-1 acts not only as a co-mitogen with EGF but also as a mitogen alone, and that its action is mediated through activation of ET_A receptors. In addition, the activity may be partly reduced by NO. Therefore, we think that ET-1 may contribute to airway remodelling, a pathophysiological hallmark of asthma.