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.
Iwagoe
H
H
Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Kohrogi
H
H
Fujii
K
K
Hamamoto
J
J
Hirata
N
N
Ando
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010047:Ovalbumin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D014132:Trachea / Q000502:physiology*
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D006632:Histamine; D010047:Ovalbumin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D000109:Acetylcholine