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.
Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
H
H
Iwagoe
H
H
Kohrogi
K
K
Fujii
J
J
Hamamoto
N
N
Hirata
M
M
Ando
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