Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction

Maya Hayashi, Shunichi Kajioka, Momoe Itsumi, Ryosuke Takahashi, Nouval Shahab, Takao Ishigami, Masahiro Takeda, Noriyuki Masuda, Akito Yamaguchi, Seiji Naito

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10 Citations (Scopus)

Abstract

Objectives To clarify the effect of cAMP on the Ca2+-sensitized smooth muscle contraction in human detrusor, as well as the role of novel exchange protein directly activated by cAMP (Epac) in cAMP-mediated relaxation. Materials and Methods All experimental protocols to record isometric tension force were performed using α-toxin-permeabilized human detrusor smooth muscle strips. The mechanisms of cAMP-mediated suppression of Ca2+ sensitization activated by 10 μm carbachol (CCh) and 100 μm GTP were studied using a selective rho kinase (ROK) inhibitor, Y-27632, and a selective protein kinase C (PKC) inhibitor, GF-109203X. The relaxation mechanisms were further probed using a selective protein kinase A (PKA) activator, 6-Bnz-cAMP and a selective Epac activator, 8-pCPT-2′-O-Me-cAMP. Results We observed that CCh-induced Ca2+ sensitization was inhibited by cAMP in a concentration-dependent manner. GF-109203X (10 μm) but not Y-27632 (10 μm) significantly enhanced the relaxation effect induced by cAMP (100 μm). 6-Bnz-cAMP (100 μm) predominantly decreased the tension force in comparison with 8-pCPT-2′-O-Me-cAMP (100 μm). Conclusions We showed that cAMP predominantly inhibited the ROK pathway but not the PKC pathway. The PKA-dependent pathway is dominant, while Epac plays a minor role in human detrusor smooth muscle Ca2+ sensitization.

Original languageEnglish
Pages (from-to)179-191
Number of pages13
JournalBJU international
Volume117
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Urology

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    Hayashi, M., Kajioka, S., Itsumi, M., Takahashi, R., Shahab, N., Ishigami, T., Takeda, M., Masuda, N., Yamaguchi, A., & Naito, S. (2016). Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction. BJU international, 117(1), 179-191. https://doi.org/10.1111/bju.13180