Novel effect of 2-aminoethoxydiphenylborate through inhibition of calcium sensitization induced by Rho kinase activation in human detrusor smooth muscle

Nouval Shahab, Shunichi Kajioka, Ryosuke Takahashi, Maya Hayashi, Shinsuke Nakayama, Kazuyuki Sakamoto, Masahiro Takeda, Noriyuki Masuda, Seiji Naito

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Since the introduction of 2-aminoethoxydiphenylborate (2-APB) as a membrane permeable modulator of inositol (1,4,5)-trisphosphate receptors, subsequent studies have revealed additional actions of this chemical on multiple Ca 2+-permeable ionic channels in the plasma membrane. However, no reports have yet examined 2-APB as a modulator targeting contractile machinery in smooth muscle, independent of Ca2+ mobilization, namely Ca 2+ sensitization. Here, we assessed whether or not 2-APB affects intracellular signaling pathways of Ca2+ sensitization for contraction using α-toxin permeabilized human detrusor smooth muscle. Although contractions were induced by application of Ca2+-containing bath solutions, 2-APB had little effect on contractions induced by 1 μM Ca2+ alone but significantly reversed the carbachol-induced augmentation of Ca2+-induced contraction in the presence of guanosine triphosphate (carbachol-induced Ca2+ sensitization). The rho kinase inhibitor Y-27632 and protein kinase C inhibitor GF-109203X also reversed the carbachol-mediated Ca2+ sensitization. Additional application of 2-APB caused a small but significant further attenuation of the contraction in the presence of GF-109203X but not in the presence of Y-27632. Like carbachol, the rho kinase activator; sphingosylphosphorylcholine, protein kinase C activator; phorbol 12,13 dibutyrate, and myosin light chain phosphatase inhibitor; calyculin-A all induced Ca2+ sensitization. However, the inhibitory activity of 2-APB was limited with sphingosylphosphorylcholine- induced Ca2+ sensitization. This study revealed a novel inhibitory effect of 2-APB on smooth muscle contractility through inhibition of the rho kinase pathway.

Original languageEnglish
Pages (from-to)14-20
Number of pages7
JournalEuropean Journal of Pharmacology
Volume708
Issue number1-3
DOIs
Publication statusPublished - May 15 2013

All Science Journal Classification (ASJC) codes

  • Pharmacology

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