Effect of cholecystokinin octapeptide on diacylglyceroI-PKC signaling pathway in rat pulmonary interstitial macrophages stimulated by lipopolysaccharide

查看全文 作　　者：Shun-jiang [1,2]XU;Wei-juan [1]GAO;Bin [1]CONG;Chun-ling [1]MA;Shu-jin [1]LI;Yi-ling [1]LING;Zhen-yong [1]GU;Yu-xia [1]YAO

机构地区：[1]Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China;[2]Now in the Hebei Province Center for Disease Prevention and Control, Shijiazhuang 050021, China

出　　处：《Acta Pharmacologica Sinica》索引2005年第26卷第12期,共8页

基　　金：Project supported by the National Natural Science Foundation of China(No 30270529);the Natural Science Foundation of Hebei Province(No 303452). 摘　　要：Aim:To investigate the effect of cholecystokinin octapeptide(CCK-8)on thediacylglycerol-protein kinase C(DAG-PKC)signaling pathway in rat pulmonaryinterstitial macrophages(PIM)stimulated by lipopolysaccaride(LPS).Methods:The PIM from rat lung tissues were isolated using the collagenase digestionmethod combined with alveolar lavage and pulmonary vessel perfusion.DAGcontent and PKC activity were measured by radioenzymatic assay.The transloca-tion of PKCζ was determined by semi-quantitative immunoblot analysis.Results:CCK-8,at high concentrations(1×10^(-6)-1×10^(-5)mol/L),decreased DAG content andinhibited PKC activity and PKCζ translocation compared with that in rat restingPIM of a control group(P<0.01).LPS increased DAG content,and promoted PKCactivity and PKC~ translocation(P<0.01).CCK-8 decreased LPS-induced DAGcontent and inhibited LPS-induced PKC activity and PKCζ translocation signifi-cantly at 1×10^(-8)-1×10^(-5)mol/L(P<0.01).This inhibitory effect of CCK-8 could beabrogated partly by proglumide(non-selective CCK receptor antagonist),CR-1409(selective CCK-A receptor antagonist),and CR-2945(selective CCK-Breceptor antagonist)in a concentration-dependent manner(P<0.01).Conclusion:CCK-8 was a negative modulator of the DAG-PKC signaling pathway in rat restingPIM,which is very important for maintaining body homeostasis.It significantlyinhibited LPS-induced DAG content,PKC activity and PKCζ translocation in aconcentration-dependent manner.The CCK receptor,especially the CCK-Areceptor,might play a major role in this process. 关键词：缩胆囊素八肽信号路径肺部空洞巨噬细胞脂多糖

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Effect of cholecystokinin octapeptide on diacylglyceroI-PKC signaling pathway in rat pulmonary interstitial macrophages stimulated by lipopolysaccharide

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