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1 Department of Pharmacology, Warner-Lambert Research Institute, Morris Plains, New Jersey
Rat peritoneal mast cells were sensitized in vitro with rat reaginic serum against ovalbumin and then were washed and suspended in buffer. Disodium cromoglycate (DSCG) (0.5-20 1. µM) caused a concentration-dependent inhibition of histamine release when added with antigen; 5 µM produced a 50% inhibition. A 4-fold increase in antigen concentration did not reverse inhibition suggesting that the DSCG did not compete directly with the antigen. Preincubation of sensitized mast cells with DSCG for various times up to 20 minutes before adding antigen resulted in a time dependent loss of inhibition which followed an s-shaped curve independent of initial DSCG concentration. After 20 minutes preincubation with DSCG the extent of reinhibition with fresh DSCG added with antigen was inversely dependent on initial DSCG concentration. Evidence exists to show that loss of inhibition is not due to a change of any factor external to the cell or to the loss of active DSCG from the medium. From the stoichiometry of the inhibition/reinhibition and from the time course of loss of inhibition, it is suggested that DSCG acts indirectly, inducing the formation of an unstable species in mast cells from a precursor present in a limited amount.
Submitted on April 24, 1972
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T. Theoharides, W Sieghart, P Greengard, and W. Douglas Antiallergic drug cromolyn may inhibit histamine secretion by regulating phosphorylation of a mast cell protein Science, January 4, 1980; 207(4426): 80 - 82. [Abstract] [PDF] |
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