Effect of butyl 3-(1H-tetrazol-5-yl) oxanilate(MTB) on immunological or non-immunological histamine and SRS(-A) release from guinea-pig, monkey and human lung tissue.

We investigated the influence of butyl 3-(1H-tetrazol-5-yl) oxanilate (MTB) on the release of histamine and slow reacting substance of anaphylaxis (SRS-A) in vitro. MTB dose-dependently inhibited the release of not only histamine but also SRS-A from passively sensitized guinea-pig lung, while disodium cromoglycate (DSCG) hardly affected either release. MTB also resulted in a dose-dependent inhibition of the release of these mediators from the passively sensitized cynomolgus and rhesus monkey and that from human lung at concentrations similar to those inhibiting the release in the guinea-pig. Relatively lower inhibitory activities on the releases of both mediators from the cynomolgus monkey and human lung, but no effects on those from the rhesus monkey were observed with DSCG. MTB dose-dependently inhibited only SRS release from guinea-pig lung induced by phospholipase A2, although the compound did not show any inhibitory activity on the release of those from the calcium ionophore (A23187)-stimulated one. On the other hand, the release of SRS, but not that of histamine from the lung stimulated with A23187 as well as phospholipase A2 was inhibited by N-(3,4-dimethoxycinnamoyl)-anthranilic acid (tranilast, N-5'). From these results, MTB was a potent inhibitor of the anaphylactic release of the mediators, particularly SRS-A. It was suggested that the inhibitory mechanism of MTB is different from those of DSCG and N-5'.