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

Abstract

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.

Comparison of Cellular Mechanisms Underlying Histamine Release From Rat Mast Cells Induced by Ionic and Nonionic Radiographic Contrast Media

“…22 Briefly, the pulmonary cells were incubated with 100 mgI/mL each of RCM for 10 minutes at 37°C in the presence of 0.5 mM IBMX to prevent the degradation of cAMP. The reaction was terminated by the addition of perchloric acid to a final concentration of 0.4 M. Cells were homogenized by sonication, and then centrifuged at 10,000g for 15 minutes.…”

“…22 Briefly, various RCM solutions were diluted with Krebs-Ringer solution to 200 mgI/mL immediately before use and the solutions were preincubated at 37°C. The mast cell suspensions (2 ϫ 10 6 cells/mL) were preincubated at 37°C, and the reaction was started by mixing 0.5-mL aliquots of cell suspensions with 0.5 mL of diluted RCM solution and incubated at 37°C for 10 minutes.…”

“…9 Moreover, a variety of ionic and nonionic RCM cause histamine release from rat pulmonary mast cells, in which the effects of ionic RCM are more marked than those induced by nonionic ones. 22 The ioxaglate-induced histamine release from pulmonary mast cells is attenuated by a membrane-permeable cAMP analog dibutyryl cAMP (DBcAMP), whereas the content of cAMP in mast cells is lowered by ioxaglate. 22 Therefore, it is likely that the reduction in cellular cAMP contributes to the ionic RCM-induced histamine release.…”

“…22 The ioxaglate-induced histamine release from pulmonary mast cells is attenuated by a membrane-permeable cAMP analog dibutyryl cAMP (DBcAMP), whereas the content of cAMP in mast cells is lowered by ioxaglate. 22 Therefore, it is likely that the reduction in cellular cAMP contributes to the ionic RCM-induced histamine release. However, it is still uncertain whether the reduction in cellular cAMP content is common to ionic and nonionic RCM.…”

Clinical and Experimental Evidence for Prevention of Acute Renal Failure Induced by Radiographic Contrast Media

“…HSRs associated with these contrast agents appear to result from the release of mast cell ingredients such as histamine and tryptase (25 -28). Indeed, a number of RCM stimulate the release of these chemical mediators from isolated mast cells, in which the effects are more marked in ionic RCM than in non-ionic RCM (22,29,30). However, the contribution of osmotic pressure to the RCM-induced degranulation of mast cells is a matter of controversy (30 -32).…”