Effect of N-5' on histamine release from rat peritoneal exudate cells induced by calcium ionophore and ATP.

We studied the effect of N-(3,4-dimethoxycinnamoyl)anthranilic acid (N-5'), an orally applicable anti-allergic drug, on the histamine release induced by calcium ionophores (A23187 and X537A) and ATP from rat peritoneal exudate cells (PEC). X537A (0.1-33.3 micrograms/ml) induced histamine release in a concentration-related manner, and 2.0 micrograms/ml of X537A induced release to the same extent as allergic histamine release. Histamine release induced by 2.0 micrograms/ml of X537A increased with longer incubation time, reaching a peak of about 100% at 120 min. N-5' had no effect on histamine release induced by X537A at the concentrations used (1-1000 microM), but DSCG exhibited significant inhibition at 1-100 microM. A23187 (0.05-0.5 microgram/ml) induced histamine release in a concentration-related manner, and it seemed that 0.033 microgram/ml of A23187 induces the same degree of histamine release as the allergic one. A23187 induced rapid histamine release which attained maximum 1 min after the addition. N-5' exhibited a significant concentration-dependent inhibitory effect on histamine release induced by A23187, and DSCG also exhibited significant inhibition (10 and 1000 microM). N-5' significantly inhibited histamine release induced by 100 microM ATP. These results indicate that N-5' and DSCG effect the histamine release induced by ionophore A23187 and X537A by different manners, and they suggest the possibility that N-5' inhibits some Ca++-dependent processes in histamine release, including the influx of Ca++ into cells, which is a trigger of the A23187 and ATP effects.