Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs.

When rat mast cells loaded with fluorescent Ca2+ indicator Quin 2 were exposed to either compound 48/80 (0.1 micrograms/mL) or substance P (2 microM) at 37 degrees C for 30 seconds in a Ca-free medium, a marked increase of Quin 2 fluorescence was noticed, indicating that Ca2+ was released from the intracellular Ca store. The pixel values of the whole cell image were displayed in a three dimensional projection. When mast cells were exposed to 48/80, the fluorescent increase was reflected as an increase of height and spreading of the image. When 0.01 to 1 mM of db-cAMP was pretreated for five minutes, an increase of Quin 2 fluorescence was inhibited in a dose-dependent fashion. Theophylline pretreatment also showed a preventive effect at 1 to 5 mM. A marked inhibition of the Quin 2 signal was induced by pretreatment with 0.01 mM of terfenadine (63.4% inhibition) or ketotifen (26.6% inhibition). Disodium cromoglycate also showed a similar inhibitory effect. In the measurement of the order parameters of liposomes, the addition of either terfenadine or ketotifen into the lipids increased the parameter value, indicating they provide the membrane stabilizing action.