T. Shishibori et al., Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family, BIOCHEM J, 338, 1999, pp. 583-589
To investigate the roles of calcium-binding proteins in degranulation, we u
sed three anti-allergic drugs, amlexanox, cromolyn and tranilast, which inh
ibit IgE-mediated degranulation of mast cells, as molecular probes in affin
ity chromatography. All of these drugs, which have different structures but
similar function, scarcely bound to calmodulin in bovine lung extract, but
bound to the same kinds of calcium-binding proteins, such as the 10-kDa pr
oteins isolated in this study, calcyphosine and annexins I-V. The 10-kDa pr
oteins obtained on three drug-coupled resins and on phenyl-Sepharose were a
nalysed by reversed-phase HPLC. It was found that two characteristic 10-kDa
proteins, one polar and one less polar, were bound with all three drugs, a
lthough S100A2 (S100L), of the S100 family, was bound with phenyl-Sepharose
. The cDNA and deduced amino acid sequence proved our major polar protein t
o be identical with the calcium-binding protein in bovine amniotic fluid (C
AAF1, S100A12). The cDNA and deduced amino acid sequence of the less-polar
protein shared 95% homology with human and mouse S100A13. In addition, it w
as demonstrated that the native S100A12 and recombinant S100A12 and S100A13
bind to immobilized amlexanox. On the basis of these findings, we speculat
e that the three anti-allergic drugs might inhibit degranulation by binding
with S100A12 and S100A13.