Inhibition of mucin secretion with MARCKS-related peptide improves airway obstruction in a mouse model of asthma

Agrawal, A. ; Rengarajan, S. ; Adler, K. B. ; Ram, A. ; Ghosh, B. ; Fahim, M. ; Dickey, B. F. (2007) Inhibition of mucin secretion with MARCKS-related peptide improves airway obstruction in a mouse model of asthma Journal of Applied Physiology, 102 (1). pp. 399-405. ISSN 8750-7587

Full text not available from this repository.

Official URL:

Related URL:


Allergic asthma is associated with airway epithelial cell mucous metaplasia and mucin hypersecretion, but the consequences of mucin hypersecretion on airway function are unclear. Recently, a peptide derived from the myristoylated alanine-rich C kinase substrate protein NH2-terminal sequence (MANS) was shown to inhibit methacholine (MCh)-induced mucin secretion from airway mucous cells by >90%. We studied the effect of intranasal pretreatment with this peptide on specific airway conductance (sGaw) during challenge with MCh in mice with allergen-induced mucous cell metaplasia. sGaw was noninvasively measured in spontaneously breathing restrained mice, using a double-chamber plethysmograph. Pretreatment with MANS peptide, but not a control peptide [random NH2-terminal sequence (RNS)], resulted in partial inhibition of the fall in sGaw induced by 60 mM MCh (mean ± SE; baseline 1.15 ± 0.06; MANS/MCh 0.82 ± 0.05; RNS/MCh 0.55 ± 0.05 cmH2O/s). The protective effect of MANS was also seen in mice challenged with allergen for 3 consecutive days to increase airway hyperresponsiveness, although the degree of protection was less (baseline 1.1 ± 0.08; MANS/MCh, 0.65 ± 0.06; RNS/MCh 0.47 ± 0.03 cmH2O/s). Because routine sGaw measurement in mice includes nasal airways, the effectiveness of MANS was also confirmed in mice breathing through their mouths after nasal occlusion (baseline 0.92 ± 0.05; MANS/MCh 0.83 ± 0.06; RNS/MCh 0.61 ± 0.03 cmH2O/s). In all instances, sGaw in the MANS-pretreated group was ∼35% higher than in RNS-treated controls, and mucous obstruction accounted for ∼50% of the MCh-induced fall in sGaw. In summary, mucin secretion has a significant role in airway obstruction in a mouse model of allergic asthma, and strategies to inhibit mucin secretion merit further investigation.

Item Type:Article
Source:Copyright of this article belongs to American Physiological Society.
Keywords:Myristoylated Alanine-rich C Kinase Substrate NH2-terminus Sequence; Specific Airway Conductance; Goblet Cells
ID Code:66034
Deposited On:21 Oct 2011 03:32
Last Modified:21 Oct 2011 03:32

Repository Staff Only: item control page