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Loss of M2 and M3 muscarinic receptor function in double mutant mice eliminates ovalbumin‐induced airway hyperresponsiveness (870.7)
Author(s) -
Fisher John,
Vincent Sandra,
Wannas Paul,
Wess Jurgen
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.870.7
Subject(s) - ovalbumin , muscarinic acetylcholine receptor , alum , adjuvant , mutant , chemistry , immunology , sensitization , eosinophil , receptor , medicine , endocrinology , immune system , biochemistry , asthma , gene , organic chemistry
Mutant murine models lacking specific muscarinic receptor (MR) subtypes are a primary tool to explore MR biology in health and disease, due to the lack of selective antagonists. Since both M2R and M3R subtypes are involved in the vagal control of airway responsiveness (AR; FASEB J 18:711,2004), we examined the impact of combined loss of M2R and M3R function on the development of AHR in M2R ‐/‐ /M3R ‐/‐ double mutant mice. AR was assessed in 12 mutant mice divided into an ovalbumin (OVA) sensitization group (n=6; OVA‐Alum adjuvant i.p. day 0 and 7 plus aerosol exposure days14‐16) and an Alum adjuvant control group (n=6; Alum). Since M2R ‐/‐ /M3R ‐/‐ double mutants show no cholinergic contractile responses, we performed a 5‐hydroxytryptamine (5‐HT) i.v. dose‐response challenge (5‐100 ug/kg) for respiratory system resistance (Rrs) to assess AR and bronchioalveolar lavage (BAL) to assess inflammatory cells. The Rrs response was not different between groups (max increase OVA 339% + 32 sem vs Alum 301% + 28; p>0.05), although the BAL eosinophil count was significantly greater in the OVA group (25% + 5) compared to the Alum (0.1% + 0.08). Our results suggest that M2R/M3R functions are critically involved in the development of OVA‐induced AHR. Grant Funding Source : Supported by Canadian Institutes for Health Research (MOP81211), Intramural Research Pgm NIDDKD, NIH