Sustained muscle contraction induced by agonists, growth factors, and Ca(2+) mediated by distinct PKC isozymes.
Sustained muscle contraction induced by agonists, growth factors, and Ca(2+) mediated by distinct PKC isozymes.
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由不同 PKC 同工酶介导的激动剂、生长因子和 Ca(2) 诱导的持续肌肉收缩。
DOI：
10.1152/ajpgi.2000.279.1.g201
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Makhlouf,GM
中科院分区：
文献类型：
--
作者：
Murthy,KS;Grider,JR;Kuemmerle,JF;Makhlouf,GM
本文研究了蛋白激酶C（PKC）在肠环肌和肠纵肌细胞持续收缩中的作用。激动剂（CCK-8和neuromedin C）诱导的初始收缩被1）Ca 2+动员抑制剂（新霉素和二甲基二十碳二烯酸）、2）calmidazolium和3）肌球蛋白轻链（MLC）激酶（MLCK）抑制剂KT-5926所消除。相反，持续收缩不受这些抑制剂的影响，但被1）PKC抑制剂白屈菜红碱和calphostin C，2）PKC-ε抗体和3）假底物PKC-ε抑制剂所消除。GDPβS同时抑制初始和持续收缩，而Gαq/11抗体仅抑制初始收缩，这意味着持续收缩依赖于不同G蛋白的激活。钙磷蛋白C、PKC-α、β、γ抗体和假底物PKC-α抑制剂可抑制表皮生长因子诱导的持续收缩。Ca 2+（0.4 μM）诱导透化肌细胞的初始收缩（可被钙调蛋白和MLCK抑制剂阻断）和持续收缩（可被钙磷蛋白C和PKC-α，β，γ抗体阻断）。因此，由Ca 2+、激动剂和生长因子诱导的初始收缩由MLCK介导，而持续收缩由特异性Ca 2+依赖性和非依赖性PKC同工酶介导。G蛋白偶联受体通过不同的G蛋白与PKC激活相关。
The role of protein kinase C (PKC) in sustained contraction was examined in intestinal circular and longitudinal muscle cells. Initial contraction induced by agonists (CCK-8 and neuromedin C) was abolished by1) inhibitors of Ca2+mobilization (neomycin and dimethyleicosadienoic acid),2) calmidazolium, and3) myosin light chain (MLC) kinase (MLCK) inhibitor KT-5926. In contrast, sustained contraction was not affected by these inhibitors but was abolished by1) the PKC inhibitors chelerythrine and calphostin C,2) PKC-ε antibody, and3) a pseudosubstrate PKC-ε inhibitor. GDPβS abolished both initial and sustained contraction, whereas a Gαq/11antibody inhibited only initial contraction, implying that sustained contraction was dependent on activation of a distinct G protein. Sustained contraction induced by epidermal growth factor was inhibited by calphostin C, PKC-α,β,γ antibody, and a pseudosubstrate PKC-α inhibitor. Ca2+(0.4 μM) induced an initial contraction in permeabilized muscle cells that was blocked by calmodulin and MLCK inhibitors and a sustained contraction that was blocked by calphostin C and a PKC-α,β,γ antibody. Thus initial contraction induced by Ca2+, agonists, and growth factors is mediated by MLCK, whereas sustained contraction is mediated by specific Ca2+-dependent and -independent PKC isozymes. G protein-coupled receptors are linked to PKC activation via distinct G proteins.