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- W2166268488 abstract "In this thesis, the effects of the two calcium -like peptides CALP1 and CALP2 on severalcell types involved in asthma are examined. Furthermore, we tested the effects of thesepeptides in a guinea pig model for allergic asthma.Calcium is a key secondary messenger, whose function is tightly regulated by thecalcium-sensing regulatory protein calmodulin (CaM). CALPs are peptides whichspecifically bind to the calcium -binding sites, the EF-hands, of CaM. Specific modulationof calcium and/or CaM-regulated processes provides insights into processes such ascell signalling. Specifically, CaM modulates the intracellular calcium concentration, sinceCaM regulates the opening and closing of calcium channels present in non-excitablecells.Asthma is a chronic airway disease characterized by airway obstruction, airwayhyperresponsiveness and most importantly, inflammation. The disease affects about10% of the population, and the prevalence is rising in many parts of the world, especiallyin children. Cells involved in the pathophysiology of asthma include airway epithelialcells, mast cells and inflammatory cells.In this thesis we show that CALP1 blocks mast cells mediator release, inhibits therelease of epithelium-derived relaxing factors and presumably attenuates radicalproduction by alveolar macrophages in vivo. CALP2, on the other hand, blocks mast cellmediator release, increases the release of NO by airway epithelial cells and markedlyincreases radical production by alveolar macrophages in vitro, and most likely also invivo. Taken together, these peptides have both beneficial and detrimental effects oncells involved in the pathogenesis of asthma. Thus, neither CALP1 nor CALP2 seem tobe candidates for therapeutic interventions in asthma. However, although more researchhas to be performed to elucidate the exact mechanism of action of these peptides, someindirect evidence has been obtained that store-operated calcium channels are crucial inthis mechanism. Therefore, specific modulation of store-operated calcium influx might bea target for future therapy against asthma. CALPs can serve as useful tool to furtherexplore the role of these calcium channels in asthma." @default.
- W2166268488 created "2016-06-24" @default.
- W2166268488 creator A5014615882 @default.
- W2166268488 date "2002-12-04" @default.
- W2166268488 modified "2023-09-26" @default.
- W2166268488 title "Calcium sensors as new therapeutic targets for asthma" @default.
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