Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction. (2nd July 2015)

• Record Type: Journal Article
• Authors: Hayashi, Maya; Kajioka, Shunichi; Itsumi, Momoe; Takahashi, Ryosuke; Shahab, Nouval; Ishigami, Takao; Takeda, Masahiro; Masuda, Noriyuki; Yamaguchi, Akito; Naito, Seiji
• Is Part Of: BJU international. Volume 117:Number 1(2016:Jan.)
• Page Start: 179
• Page End: 191
• Publication Date: 2015-07-02
• Subjects: human detrusor smooth muscle -- permeabilization -- α‐toxin -- cAMP -- calcium sensitization -- rho kinase; Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.13180
• Languages: English
• ISSNs: 1464-4096

Abstract

Abstract : Objectives: To clarify the effect of cAMP on the Ca 2+ ‐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 Ca 2+ 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 Ca 2+ 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 Ca 2+ sensitization.