title: The potential interaction of MARCKS-related peptide and diltiazem on acrolein-induced airway mucus hypersecretion in rats.
abstract: Airway mucus hypersecretion is recognized as a pathophysiological feature of airway inflammation. Ca2+ entry and myristoylated alanine-rich C kinase substrate translocation are considered as important factors in such process. To investigate the potential interaction of myristoylated alanine-rich C kinase substrate (MARCKS)-related peptide and diltiazem on acrolein-induced airway mucus hypersecretion in rats, rat model of airway mucus hypersecretion was established by inhalation of acrolein on 12 consecutive days. MARCKS-related peptide, diltiazem, saline or the combination (MARCKS-related peptide+diltiazem) was intratracheally administered respectively. The rats were received pilocarpine to stimulate mucus release before sacrifices. The expression of Mucin5ac in bronchoalveolar lavage fluid (BALF) was measured by ELISA. Intracellular Muc5ac level was detected by immunohistochemical staining and western-blot. Muc5ac mRNA in lung was analyzed by RT-PCR.
  
  
  RESULTS
  Instillation of MARCKS-related peptide attenuated the release of Muc5ac in BALF induced by acrolein(p<0.05). Diltiazem alone had no effect on mucus hypersecretion induced by acrolein. However, the release of Muc5ac in BALF was further reduced when challenged with simultaneous instillation with MARCKS-related peptide and diltiazem, compared with MARCKS-related peptide alone (p<0.05). The intracellular level of Muc5ac in lung was increased when treated with MARCKS-related peptide alone or MARCKS-related peptide plus diltiazem (p<0.05). Nevertheless, diltiazem alone did not take effect as above.
  
  
  CONCLUSIONS
  In the model of airway mucus hypersecretion induced by acrolein, MARCKS-related peptide attenuated mucus secretion and the inhibitory effect was enhanced by diltiazem, which may be due to a further diminution of the intracellular free calcium concentration and retention of mucin within epithelial goblet cells.
authors.affiliation: Department of Respiratory Medicine, The Third People's Hospital of Chengdu, Chengdu, Sichuan 610031, China; Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: chenpengsimv@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Deng
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Jiqiong
authors.initials: J
authors.lastname: Li
authors.forename: Yulin
authors.initials: Y
authors.lastname: Feng
authors.forename: Shangfu
authors.initials: S
authors.lastname: Zhang
authors.forename: Yunyie
authors.initials: Y
authors.lastname: Nin
authors.forename: Daishun
authors.initials: D
authors.lastname: Liu
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Xuemei
authors.initials: X
authors.lastname: Ou
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wen
mesh_terms: D000171:Acrolein; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D004347:Drug Interactions; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D055271:Mucin 5AC / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; C483227:MARCKS-related peptide; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D010446:Peptide Fragments; D010862:Pilocarpine; D000171:Acrolein; D004110:Diltiazem
keywords: Airway; Diltiazem; MARCKS; Mucus hypersecretion