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Effects of cyclopiazonic acid, a novel Ca 2+ ‐ATPase inhibitor, on contractile responses in skinned ileal smooth muscle
Author(s) -
Uyama Yoshiaki,
Imaizumi Yuji,
Watanabe Minoru
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14316.x
Subject(s) - cyclopiazonic acid , caffeine , contraction (grammar) , chemistry , muscle contraction , biophysics , calcium , endoplasmic reticulum , acetylcholine , ruthenium red , inositol , endocrinology , medicine , biochemistry , biology , receptor , organic chemistry
1 Effects of cyclopiazonic acid (CPA), a specific inhibitor of the Ca 2+ ‐ATPase in sarcoplasmic reticulum (SR) of skeletal and cardiac muscles, on contractile responses induced by Ca 2+ ‐release from intracellular storage sites were examined in the longitudinal smooth muscle strip of the guinea‐pig ileum skinned with β‐escin. 2 Ca 2+ ‐loading of storage sites (Ca 2+ ‐uptake) was performed in pCa 6.3 solution. The amount of Ca 2+ taken up was monitored by use of the amplitude of contraction following application of 25 m m caffeine or 25 μ m inositol 1,4,5‐trisphosphate (IP 3 ). 3 Contractile responses to caffeine or IP 3 were reduced or abolished when the preceding Ca 2+ ‐uptake was performed in the presence of 0.1–10 μ m CPA. The dose of CPA required to inhibit the contraction induced by caffeine or IP 3 by 50% was approximately 0.6 μ m . The CPA‐sensitive Ca 2+ ‐uptake completely depended upon the presence of ATP in the solution during Ca 2+ ‐uptake. 4 When 1 μ m CPA was added after Ca 2+ ‐uptake, the subsequent caffeine‐ or IP 3 ‐induced contraction was not significantly affected by the presence of CPA. 5 Acetylcholine‐induced contraction was also almost abolished when the preceding Ca 2+ ‐uptake was performed in the presence of 10 μ m CPA. 6 The relationship between pCa and contraction was not affected by the presence of 10 μ m CPA in skinned fibres where Ca 2+ storage sites had been destroyed by treatment with A23187. The enhancement of contraction in pCa 6.0 solution by calmodulin was not affected by 10 μ m CPA. 7 These results suggest that CPA selectively inhibits ATP‐dependent Ca 2+ ‐uptake into intracellular storage sites in skinned ileal smooth muscle strips. CPA appears to be a potent, reversible, and very specific inhibitor of the Ca 2+ ‐pump in the storage sites of smooth muscle, and is an extremely valuable pharmacological tool.