Open AccessEffect of cholecystokinin octapeptide on diacylglycerol‐PKC signaling pathway in rat pulmonary interstitial macrophages stimulated by lipopolysaccharide 1
Author(s) -
XU Shunjiang,
GAO Weijuan,
CONG Bin,
MA Chunling,
LI Shujin,
LING Yiling,
GU Zhenyong,
YAO Yuxia
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00217.x
Subject(s) - diacylglycerol kinase , protein kinase c , cholecystokinin , endocrinology , chemistry , medicine , signal transduction , microbiology and biotechnology , biology , biochemistry , receptor
Abstract Aim: To investigate the effect of cholecystokinin octapeptide (CCK‐8) on the diacylglycerol‐protein kinase C (DAG‐PKC) signaling pathway in rat pulmonary interstitial macrophages (PIM) stimulated by lipopolysaccaride (LPS). Methods: The PIM from rat lung tissues were isolated using the collagenase digestion method combined with alveolar lavage and pulmonary vessel perfusion. DAG content and PKC activity were measured by radioenzymatic assay. The translocation 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 and inhibited PKC activity and PKCζ translocation compared with that in rat resting PIM of a control group ( P <0.01). LPS increased DAG content, and promoted PKC activity and PKCζ translocation ( P <0.01). CCK‐8 decreased LPS‐induced DAG content and inhibited LPS‐induced PKC activity and PKCζ translocation significantly at 1×10 −8 ‐1×10 −5 mol/L ( P <0.01). This inhibitory effect of CCK‐8 could be abrogated partly by proglumide (non‐selective CCK receptor antagonist), CR‐1409 (selective CCK‐A receptor antagonist), and CR‐2945 (selective CCK‐B receptor antagonist) in a concentration‐dependent manner ( P <0.01). Conclusion: CCK‐8 was a negative modulator of the DAG‐PKC signaling pathway in rat resting PIM, which is very important for maintaining body homeostasis. It significantly inhibited LPS‐induced DAG content, PKC activity and PKCζ translocation in a concentration‐dependent manner. The CCK receptor, especially the CCK‐A receptor, might play a major role in this process.