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 inhib itor, herbimycin A and genistein, on antigen-induced tracheal contract ion and antigen-induced histamine release from the trachea in sensitiz ed guinea pigs in vitro. Herbimycin A (1-10 mu M) and genistein (1-10 mu M) significantly inhibited antigen-induced tracheal contraction, co mpared with control. Additionally, herbimycin A (1-10 mu M) and genist ein (3-10 mu M) significantly inhibited antigen-induced histamine rele ase from the trachea in a concentration-dependent manner, compared wit h control. On the contrary, herbimycin A and genistein did not suppres s acetylcholine- and histamine-induced tracheal contraction. We conclu ded that herbimycin A and genistein inhibit antigen-induced tracheal c ontraction without inhibiting smooth muscle contractility, and these i nhibitory effects are due to, at least partially, inhibiting histamine release from tracheal mast cells.