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High concentrations of landiolol, a beta(1)-adrenoceptor antagonist, stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.


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タイトル: High concentrations of landiolol, a beta(1)-adrenoceptor antagonist, stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.
著者: Shibata, Osamu / Nishioka, Kenji / Yamaguchi, Masakazu / Makita, Tetsuji / Sumikawa, Koji
発行日: 2008年 2月
出版者: Springer Japan
引用: Journal of anesthesia, 22(1), pp.21-26; 2008
抄録: PURPOSE: Gradually progressing contraction of airway smooth muscle is suggested to be due to the Rho-kinase signaling pathway. In our preliminary study in rat tracheas, landiolol, a beta(1)-adrenoceptor antagonist, at high doses caused gradually progressing contraction, and this contraction reached a plateau after 20 min. Therefore, this study was carried out to clarify whether landiolol could stimulate the Rho-kinase pathway or the phosphatidylinositol (PI) response in the rat trachea. METHODS: Seventy-eight male Wistar rats weighing 250-350 g were used for the experiments. Their tracheas were cut into 3-mm-wide ring segments or 1-mm-wide slices. Measurements of isometric tension and [(3)H] inositol monophosphate (IP(1)) production were conducted, using these tracheal rings or slices. Data values are expressed as means +/- SD, and statistical significance (P < 0.05) was determined using analysis of variance (ANOVA). RESULTS: Landiolol (700 microM)-induced contraction was completely inhibited by fasudil at 30 microM, while the landiolol-induced contraction was not inhibited by 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), ketanserin, or nicardipine. Landiolol did not stimulate IP(1) production. CONCLUSION: These results suggest that high concentrations of landiolol could cause airway smooth muscle contraction through the Rho-kinase pathway, but not through the PI response coupled with muscarinic M(3) receptors, 5-HT receptors or the activation of L-type Ca(2+) channels.
キーワード: β1-adrenoceptor antagonist / Landiolol / Phosphatidylinositol response / Rho-kinase pathway / Tracheal smooth muscle
URI: http://hdl.handle.net/10069/22765
ISSN: 09138668 / 14388359
DOI: 10.1007/s00540-007-0567-1
PubMed ID: 18306009
権利: © Japanese Society of Anesthesiologists 2008. / The original publication is available at www.springerlink.com
資料タイプ: Journal Article
原稿種類: author
出現コレクション:130 学術雑誌論文

引用URI : http://hdl.handle.net/10069/22765

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