The potential interaction of MARCKS-related peptide and diltiazem on acrolin-induced airway mucus hypersecretion in rats

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. (C) 2013 Elsevier B.V. All rights reserved.