Ca2+ sensors modulate asthmatic symptoms in an allergic model for asthma.
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.
Ten Broeke
Robert
R
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
Brandhorst
Marcel C
MC
Leusink-Muis
Thea
T
Villain
Matteo
M
De Clerck
Fred
F
Blalock
J Edwin
JE
Nijkamp
Frans P
FP
Folkerts
Gert
G
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D002452:Cell Count; D015550:Cell Degranulation / Q000187:drug effects; D004195:Disease Models, Animal; D006168:Guinea Pigs; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
C420971:CALP2 protein, synthetic; D002147:Calmodulin; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D017382:Reactive Oxygen Species; C412708:calcium-like peptide CALP1; D010047:Ovalbumin; D002118:Calcium