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Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction
Author(s) -
Hayashi Maya,
Kajioka Shunichi,
Itsumi Momoe,
Takahashi Ryosuke,
Shahab Nouval,
Ishigami Takao,
Takeda Masahiro,
Masuda Noriyuki,
Yamaguchi Akito,
Naito Seiji
Publication year - 2016
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.13180
Subject(s) - contraction (grammar) , calcium , muscle contraction , detrusor muscle , sensitization , chemistry , medicine , neuroscience , smooth muscle , endocrinology , biology
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 μ m carbachol ( CC h) and 100 μ m 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 CC h‐induced Ca 2+ sensitization was inhibited by cAMP in a concentration‐dependent manner. GF ‐109203X (10 μ m ) but not Y‐27632 (10 μ m ) significantly enhanced the relaxation effect induced by cAMP (100 μ m ). 6‐Bnz‐ cAMP (100 μ m ) predominantly decreased the tension force in comparison with 8‐ pCPT ‐2′‐ O ‐Me‐ cAMP (100 μ m ). 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.