EFFECTS OF CYCLOPIAZONIC ACID, A NOVEL CA-2+-ATPASE INHIBITOR, ON CONTRACTILE RESPONSES IN SKINNED ILEAL SMOOTH-MUSCLE
EFFECTS OF CYCLOPIAZONIC ACID, A NOVEL CA-2+-ATPASE INHIBITOR, ON CONTRACTILE RESPONSES IN SKINNED ILEAL SMOOTH-MUSCLE
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DOI：
10.1111/j.1476-5381.1992.tb14316.x
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发表时间：
1992-05-01
影响因子：
7.3
通讯作者：
WATANABE, M
中科院分区：
文献类型：
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作者：
UYAMA, Y;IMAIZUMI, Y;WATANABE, M
1观察了骨骼肌和心肌肌浆网Ca~（2+）-ATP酶的特异性抑制剂环匹阿尼酸（CPA）对β-七叶皂苷处理的豚鼠回肠纵行平滑肌条由胞内贮钙位点释放Ca~（2+）引起的收缩反应的影响。通过应用25 mM咖啡因或25 μ M肌醇1，4，5-三磷酸盐（IP3）后的收缩幅度监测摄取的Ca2+的量。3当在0.1 - 10 μ M CPA存在下进行先前的Ca2+摄取时，对咖啡因或IP3的收缩反应减少或消除。抑制由咖啡因或IP 3诱导的收缩50%所需的CPA剂量约为0.6 μ M。CPA敏感的Ca 2+摄取完全依赖于Ca 2+摄取期间溶液中ATP的存在。4当在Ca 2+摄取后加入1 μ M CPA时，随后的咖啡因或IP3诱导的收缩不受CPA的影响。5乙酰胆碱诱导的收缩也几乎被取消时，在10 μ-M CPA.6 pCa和收缩之间的关系不受带皮纤维中10 μ M CPA的存在的影响，其中Ca2+储存位点已被A23187处理破坏。在pCa 6.0溶液中，钙调素对收缩的增强作用不受10 μ M CPA的影响。7这些结果表明，CPA选择性地抑制了带皮回肠平滑肌条中ATP依赖性Ca 2+摄取进入细胞内储存位点。CPA似乎是一种有效的，可逆的，和非常具体的抑制剂的Ca 2 +-泵储存网站的平滑肌，是一个非常有价值的药理学工具。
1 Effects of cyclopiazonic acid (CPA), a specific inhibitor of the Ca2+-ATPase in sarcoplasmic reticulum (SR) of skeletal and cardiac muscles, on contractile responses induced by Ca2+-release from intracellular storage sites were examined in the longitudinal smooth muscle strip of the guinea-pig ileum skinned with beta-escin.2 Ca2+-loading of storage sites (Ca2+-uptake) was performed in pCa 6.3 solution. The amount of Ca2+ taken up was monitored by use of the amplitude of contraction following application of 25 mM caffeine or 25-mu-M inositol 1,4,5-trisphosphate (IP3).3 Contractile responses to caffeine or IP3 were reduced or abolished when the preceding Ca2+-uptake was performed in the presence of 0.1-10-mu-M CPA. The dose of CPA required to inhibit the contraction induced by caffeine or IP3 by 50% was approximately 0.6-mu-M. The CPA-sensitive Ca2+-uptake completely depended upon the presence of ATP in the solution during Ca2+-uptake.4 When 1-mu-M CPA was added after Ca2+-uptake, the subsequent caffeine- or IP3-induced contraction was not significantly affected by the presence of CPA.5 Acetylcholine-induced contraction was also almost abolished when the preceding Ca2+-uptake was performed in the presence of 10-mu-M CPA.6 The relationship between pCa and contraction was not affected by the presence of 10-mu-M CPA in skinned fibres where Ca2+ 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-mu-M CPA.7 These results suggest that CPA selectively inhibits ATP-dependent Ca2+-uptake into intracellular storage sites in skinned ileal smooth muscle strips. CPA appears to be a potent, reversible, and very specific inhibitor of the Ca2+-pump in the storage sites of smooth muscle, and is an extremely valuable pharmacological tool.