Inhibitory Effects of Oxatomide on Intracellular Ca Mobilization, Ca Uptake and Histamine Release, Using Rat Peritoneal Mast Cells

Abstract

Oxatomide at concentrations of 0.01––10 μM inhibited not only an increase in ⁴⁵Ca uptake but also the intracellular Ca²⁺ release induced by compound 48/80 in rat peritoneal mast cells. At higher concentrations, ketotifen or other calcium antagonists caused similar inhibitory effects. However, the inhibitory effect of oxatomide on the ⁴⁵Ca uptake into rat neonatal heart cells was much weaker than that of verapamil. Through image processing of quin 2-stained mast cells, it was revealed that oxatomide inhibited Ca²⁺ release from the intracellular store. Although oxatomide alone did not affect cAMP and cGMP contents in sensitized guinea pig lung samples, the drug effectively prevented changes in the nucleotide contents evoked by antigen challenge. These results suggest that the inhibitory effect of oxatomide on histamine release may be caused by a combination of (1) prevention of Ca uptake, which is highly selective toward mast cells; (2) inhibition of Ca²⁺ release from the intracellular Ca store, and (3) elevation of the cAMP content in mast cells.

Antiallergic Effect of Epinastine (WAL 801 CL) on Immediate Hypersensitivity Reactions: (I) Elucidation of the Mechanism for Histamine Release Inhibition

“…We have previously reported that oxatomide is effective in the same concentration range in inhibiting both increases in 4 5 C a uptake and intracellular Ca2+ release induced by compound 48/80 in rat peritoneal mast cells (7). Thus, it seems possible that the inhibition of Ca2+ incorporation into guinea pig lung mast cells and of Ca2+ releasc from the intracellular Ca store of rat mast cells caused by epinastine takes place in almost the same concentration range, which is also effective in inhibiting histamine release.…”

“…Intracellular Ca2+ conccntration was measured according to the mcthod described in a previous paper (7). In bricl', rat peritoneal mast cells washcd with PBS were suspended in 5 pM of quin 2/AM, and incubatcd for 60 min at 37°C.…”

Inhibitory Effect of Egualen Sodium: A New Stable Derivative of Azulene on Histamine Release from Mast Cell-Like Cells in the Stomach

“…Histamine release from lung pieces of actively sensitized guinea pigs was measured according to the method previously described [17]. Male Hartley guinea pigs, weighing 350-400 g, were immunized according to the method of Mota et al [18].…”

Effect of Oxatomide Nasal Spray on Experimental Allergic Rhinitis in Guinea Pigs and Rats

“…It is considered that the inhibitory effects on chemical media tors, such as histamine and leukotrienes, of oxatomide [6,7] and the inhibitory effect on histamine release of oxatomide [2][3][4][5] were exhibited by its intranasal administration of ox atomide nasal spray. Accordingly, oxatomide nasal spray is expected to be effective against two of the three main symp toms of allergic rhinitis, i.e., rhinorrhea and nasal conges tion; the latter is due to edema caused by plasma leakage.…”