Actions and cross-reactivity of antiallergic agents and a calcium channel antagonist on rat peritoneal mast cells. Difference in the action mechanisms and cross-reactivity among the agents

Abstract

The actions of the antiallergic agents, disodium chromoglycate (DSCG), tranilast and ketotifen, and of a calcium channel antagonist, nicardipine, and cross-reactivity among the agents were examined by observing the inhibition of 45Ca uptake and histamine release in rat mast cells stimulated by antigen and compound 48/80 (comp. 48/80). 1) All agents inhibited 45Ca uptake and histamine release in mast cells stimulated by antigen. The inhibition of 45Ca uptake by the antiallergic agents paralleled the inhibition of histamine release, while nicardipine inhibition of 45Ca uptake was stronger than its inhibition of histamine release. 2) The action of DSCG on 45Ca uptake and histamine release was significantly decreased in cells stimulated with antigen and phosphatidylserine (PS), while tranilast inhibition of histamine release was not affected by the addition of PS despite a significant decrease in the inhibition of 45Ca uptake. 3) The inhibitory effect of DSCG and tranilast was significantly lower in mast cells stimulated by comp. 48/80 than in the cells stimulated by antigen. 4) Tachyphylaxis was observed in cells re-exposed to DSCG and tranilast following previous exposure to the agents. 5) Cross-reactivity was found between DSCG and tranilast.

Effect of topical application of Brazilian propolis on scratching behavior induced by compound 48/80 in mice

“…On the other hand, we demonstrated in an in vitro study that propolis inhibited histamine release from rat mast cells induced by compound 48/80. The effect of propolis was more potent than representative anti-allergic drugs, tranilast and disodium chromoglycate [11]. These findings suggest that the inhibitory effects of propolis on scratching behavior and vascular permeability induced by compound 48/80 observed in the late phase may be due to a mast cell-dependent mechanism.…”

Role of histamine and acid back-diffusion in modulation of gastric microvascular permeability and hemorrhagic ulcers in Salmonella typhimurium-infected rats

“…On the other hand, activation of H 2 receptors locating on cells of gastric mucosa and big blood vessels may increase intracellular cAMP and decrease intracellular calcium levels (Hill, 1990;Tanizaki et al, 1992). Lack of inhibitory effect of ranitidine on increased gastric microvascular permeability in Salmonella typhi-infected rat stomachs is probably associated with H 2 receptors that mainly being present on the gastric vascular smooth muscle cells instead.…”

“…Ketotifen is shown to inhibit cellular [ 45 Ca] uptake and histamine biosynthesis in mast cells stimulated by antigen (Tanizaki et al, 1992). In the gastrointestinal tract, histamine may cause a potent contraction of the smooth muscle cells and gastric mucosal internal leak (Demling et al, 1982) that may contribute to plasma protein, electrolyte and water loss.…”

Suppression of Proliferative Responses of Lymphocytes to Food Antigens by an Anti-Allergic Drug, Ketotifen Fumarate, in Patients with Food-Sensitive Atopic Dermatitis

“…These results sug gest that ketotifen inhibits food antigen-specific prolifer ative responses of PBMCs in patients with food-sensitive AD. Tanizaki et al [9] reported that ketotifen inhibited the Ca2+ uptake into cells. Therefore, ketotifen may in hibit part of the processes ranging from antigen recog nition by T-cell receptors to Ca2+-dependent signal trans duction in T-cell responses to the food antigen.…”