Analysis of airway hyperresponsiveness using in vitro contraction model

Masahiro Oike, Yushi Ito

Research output: Contribution to journalArticle

Abstract

We have established an in vitro model of airway hyperresponsiveness, using bovine tracheal smooth muscle cells (BTSMC)-embedded collagen gel lattice. When the gel was pretreated with lysophosphatidic acid (LPA), which activates small G-protein RhoA, ATP- and high K+ solution-induced gel contraction was significantly augmented. This was not due to the modulation of Ca 2+-mobilizing properties, since ATP- and high K+-induced Ca2+ transients were not different significantly between control and LPA-treated BTSMC. Y-27632, an inhibitor of Rho-kinase, suppressed the LPA-induced augmentation of gel contraction, whereas it did not inhibit the contraction of control gels. Theophylline (>1μM) reversed the LPA-induced augmentation of gel contraction, whereas it inhibited control gel contraction only with a very high concentration (100μM). Theophylline suppressed the LPA-induced membrane translocation of RhoA, indicating that it prevented airway hyperresponsiveness by inhibiting RhoA. We conclude from these results that theophylline inhibits LPA-induced, RhoA/Rho-kinase-mediated hyperresponsiveness of tracheal smooth muscle cells.

Original languageEnglish
JournalFolia Pharmacologica Japonica
Volume122
Issue numberSUPPL. 1
Publication statusPublished - Dec 1 2003

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Gels
Theophylline
Smooth Muscle Myocytes
rho-Associated Kinases
Adenosine Triphosphate
Monomeric GTP-Binding Proteins
In Vitro Techniques
lysophosphatidic acid
Collagen
Membranes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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Analysis of airway hyperresponsiveness using in vitro contraction model. / Oike, Masahiro; Ito, Yushi.

In: Folia Pharmacologica Japonica, Vol. 122, No. SUPPL. 1, 01.12.2003.

Research output: Contribution to journalArticle

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