title: Effect of cholecystokinin octapeptide on diacylglycerol-PKC signaling pathway in rat pulmonary interstitial macrophages stimulated by lipopolysaccharide.
abstract: OBJECTIVE
  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 PKCzeta was determined by semi-quantitative immunoblot analysis.
  
  
  RESULTS
  CCK-8, at high concentrations (1 x 10(-6) - 1 x 10(-5) mol/L), decreased DAG content and inhibited PKC activity and PKCzeta translocation compared with that in rat resting PIM of a control group (P< 0.01). LPS increased DAG content, and promoted PKC activity and PKCzeta translocation (P< 0.01). CCK-8 decreased LPS-induced DAG content and inhibited LPS-induced PKC activity and PKCzeta translocation significantly at 1 x 10(-8) - 1 x 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).
  
  
  CONCLUSIONS
  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 PKCzeta translocation in a concentration-dependent manner. The CCK receptor, especially the CCK-A receptor, might play a major role in this process.
authors.affiliation: Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Shun-Jiang
authors.initials: SJ
authors.lastname: Xu
authors.forename: Wei-Juan
authors.initials: WJ
authors.lastname: Gao
authors.forename: Bin
authors.initials: B
authors.lastname: Cong
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Ma
authors.forename: Shu-Jin
authors.initials: SJ
authors.lastname: Li
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Ling
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Gu
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Yao
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D012844:Sincalide / Q000494:pharmacology*; D000099221:Protein Kinase C zeta
chemical_list: D001569:Benzodiazepines; D004075:Diglycerides; D007527:Isoenzymes; D008070:Lipopolysaccharides; D011377:Proglumide; D011493:Protein Kinase C; D011949:Receptors, Cholecystokinin; D012844:Sincalide; D000099221:Protein Kinase C zeta; C011439:1,2-diacylglycerol; C116183:CR 2945; C048181:lorglumide