Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 367, Issue 4, pp 364–371

Roles of intracellular Ca2+ and cyclic AMP in mast cell histamine release induced by radiographic contrast media

  • Mami Saito
  • Yoshinori Itoh
  • Takahisa Yano
  • Toshiaki Sendo
  • Takeshi Goromaru
  • Naoko Sakai
  • Ryozo Oishi
Original Article


Mast cell histamine release is considered to be associated with the etiology of anaphylactoid reactions to iodinated radiographic contrast media (RCM). In the present study, the effects of various ionic and non-ionic RCM on histamine release from mast cells were compared, and the possible mechanisms of the histamine release were subsequently determined. Both ionic (ioxaglate and amidotrizoate) and non-ionic (iohexol, ioversol, iomeprol, iopamidol and iotrolan) RCM increased histamine release from the dissociated rat pulmonary cells, whereby ionic materials were more potent than non-ionic agents. There was no significant correlation between the extent of histamine release and the osmolarity of each RCM solution. In addition, hyperosmotic mannitol solution (1000 mOsm/kg) caused no marked histamine release. Thus, it is unlikely that the hyperosmolarity of RCM solutions contributes to the histamine release. RCM also stimulated, but to a lesser extent, the histamine release from rat peritoneal cells. The RCM-induced histamine release from both types of cells was inhibited by dibutyl cyclic AMP or combined treatment with forskolin and 3-isobutyl-1-methylxanthine. Corresponding to these results, RCM markedly reduced the cellular cyclic AMP content. On the other hand, the removal of intracellular but not the extracellular Ca2+ attenuated the RCM-induced mast cell histamine release. From these findings, it is suggested that the decrease in cellular cyclic AMP content and an increase in intracellular Ca2+ contribute at least in part to the RCM-induced mast cell histamine release.


Radiographic contrast media Pulmonary mast cells Peritoneal mast cells Histamine Intracellular calcium Osmolarity 


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Mami Saito
    • 1
  • Yoshinori Itoh
    • 1
  • Takahisa Yano
    • 1
  • Toshiaki Sendo
    • 1
  • Takeshi Goromaru
    • 1
  • Naoko Sakai
    • 1
  • Ryozo Oishi
    • 1
  1. 1.Department of Hospital Pharmacy, Faculty of MedicineKyushu UniversityHigashi-kuJapan

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