Inhibitory effect of tyrosine kinase inhibitors on antigen-induced tracheal contraction and histamine release in guinea pigs.

We examined the effect of two different types of tyrosine kinase inhibitor, herbimycin A and genistein, on antigen-induced tracheal contraction and antigen-induced histamine release from the trachea in sensitized guinea pigs in vitro. Herbimycin A (1-10 microM) and genistein (1-10 microM) significantly inhibited antigen-induced tracheal contraction, compared with control. Additionally, herbimycin A (1-10 microM) and genistein (3-10 microM) significantly inhibited antigen-induced histamine release from the trachea in a concentration-dependent manner, compared with control. On the contrary, herbimycin A and genistein did not suppress acetylcholine- and histamine-induced tracheal contraction. We concluded that herbimycin A and genistein inhibit antigen-induced tracheal contraction without inhibiting smooth muscle contractility, and these inhibitory effects are due to, at least partially, inhibiting histamine release from tracheal mast cells.