Abstract:
:We previously described two novel peptides, Ca2+-like peptide (CALP) 1 and CALP2, which interact with Ca2+-binding EF hand motifs, and therefore have the characteristics to define the role of the Ca2+-sensing regulatory protein calmodulin in asthma. In the present study, the effects of the calcium-like peptides were investigated in an animal model for allergic asthma. For that purpose, sensitized guinea pigs were intratracheally pretreated with CALP1 or CALP2. Thirty minutes later, the animals were challenged with aerosolized ovalbumin. Acute bronchoconstriction was measured as well as characteristic features of asthma 6 and 24 hours (h) after challenge. Neither CALP1 nor CALP2 prevented the anaphylactic response elicited by ovalbumin challenge. However, CALP1 pretreatment attenuated the influx of inflammatory cells in the lungs 6 h after challenge. Furthermore, radical production by these cells was diminished both 6 and 24 h after challenge. Moreover, CALP1 completely inhibited airway hyperresponsiveness in vitro 24 h after challenge. We conclude that CALP1, as a selective calmodulin agonist, inhibits the development of asthmatic features probably via the attenuation of mast cell degranulation and radical production. Specific modulation of calmodulin activity might therefore be a potential new target for the treatment of allergic asthma.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Ten Broeke R,Brandhorst MC,Leusink-Muis T,Villain M,De Clerck F,Blalock JE,Nijkamp FP,Folkerts Gdoi
10.1016/s0014-2999(03)02016-8keywords:
subject
Has Abstractpub_date
2003-08-22 00:00:00pages
151-7issue
1-2eissn
0014-2999issn
1879-0712pii
S0014299903020168journal_volume
476pub_type
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