Induction of histamine release and calmodulin antagonism are two distinct properties of compound 4880

Abstract Compound 48 80 , a mixture of oligomers, was fractionated by passing it in the presence of Ca 2+ over a calmodulin-Sepharose column. The fraction not retained by the gel was shown by mass spectrometry to consist mainly of trimers, tetramers and pentamers. A second fraction consisting of hexamers and heptamers was eluted from the column at high ionic strength in the presence of Ca 2+ . Finally, in the presence of EGTA at high ionic strength, a third fraction eluted mainly consisting of higher oligomers (hexamers to dodecamers). The different fractions were characterized by testing their influence on calmodulin-sensitive Ca 2+ -transporting ATPase and their ability to elicit histamine release from mast cells. The third fraction showed the highest potency as calmodulin antagonist, however, the second fraction was the most potent in inducing histamine secretion. This would imply that the ability of compound 48 80 to evoke histamine release and to inhibit the function of calmodulin are distinct properties of the agent which are unrelated.