Inflammation Research

, Volume 45, Issue 11, pp 564–573 | Cite as

Relation between effects of a set of anti-allergic drugs on calcium pathways and membrane structure in Fc∈RI activated signal transduction

  • M. J. E. Fischer
  • J. J. C. Paulussen
  • R. Roozendaal
  • R. C. Tiemessen
  • N. J. de Mol
  • L. H. M. Janssen
Original Research Papers


The antigen induced stimulation of mast cells by aggregation of Fc∈RI receptors activates a signal transduction cascade leading to release of mediators of inflammation like histamine, arachidonic acid metabolites and cytokines. In this study we investigated a series of structurally related anti-allergic drugs, containing a common lipophilic diphenylmethyl piperazinyl tail and head groups that differ in lipophilicity. Effects of these drugs on various steps of the signal transduction cascade was investigated to gain insight into the mechanism of action of these drugs. It appeared that addition of the drugs to resting cells induced changes in the tyrosine phosphorylation of cellular proteins. The most active anti-allergics in inhibiting exocytosis, AL3264 and oxatomide, also induced the largest changes in phosphorylation. The effects of the drugs on tyrosine phosphorylation after cell activation was complex. Additionally, Ca2+ fluxes were investigated. Ca2+ efflux from the cells was negligibly influenced by the active drugs. However, the drugs inhibited influx from extracellular Ca2+, which was correlated with the effects of the drugs on inhibition of exocytosis and on membrane stabilization induced by the drugs, measured as haemolysis of erythrocytes. It is concluded that inhibition of Ca2+ influx is the major mechanism with which these drugs inhibit exocytosis and that for this effect drug-membrane interactions, possibly affecting the function of membrane embedded proteins, are of importance. Possible mechanisms including drug-membrane interactions, phosphorylation and inhibition of Ca2+ influx are discussed.

Key words

RBL-2H3 Fc∈RI Membrane Protein tyrosine phosphorylation Calcium 



cells, a subline of rat basophilic leukemia cells


the high affinity receptor for IgE


human dinitrophenyl albumin


calcium releaseactivated calcium current




ethylene glycol-bis(β-amino-ethyl ether)N,N,N′,N′-tetraacetic acid


intracellular free calcium concentration


inositol 1,4,5-trisphosphate


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Copyright information

© Birkhäuser Verlag 1996

Authors and Affiliations

  • M. J. E. Fischer
    • 1
  • J. J. C. Paulussen
    • 1
  • R. Roozendaal
    • 1
  • R. C. Tiemessen
    • 1
  • N. J. de Mol
    • 1
  • L. H. M. Janssen
    • 1
  1. 1.Department of Pharmaceutical Chemistry, Utrecht Institute for Pharmaceutical Sciences (part of the Research School Groningen Utrecht Institute for Drug Exploration (GUIDE)), Faculty of PharmacyUtrecht UniversityUtrechtThe Netherlands

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