Piceatannol, a Syk-selective tyrosine kinase inhibitor, attenuated antigen challenge of guinea pig airways in vitro.
Activation of nontransmembrane protein tyrosine kinases, such as Lyn and Syk, has been shown to be the earliest detectable signaling response to Fc receptor (Fc epsilon RI) cross-linking on mast cells leading to mast cell degranulation. The present study examined the effects of piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene, 10-100 microM), a Syk-selective tyrosine kinase inhibitor, on ovalbumin-induced anaphylactic contraction of isolated guinea pig bronchi and release of histamine and peptidoleukotrienes from chopped lung preparations. Pretreatment with piceatannol slightly suppressed ovalbumin-induced peak anaphylactic bronchial contraction but markedly (P<0.05) facilitated relaxation of the anaphylactically contracted bronchi. Piceatannol did not inhibit direct histamine-, leukotriene D(4)- or KCl-induced bronchial contraction, nor revert an existing anaphylactic bronchial contraction. Piceatannol, at 30 microM and above, significantly (P<0.05) prevented ovalbumin-induced release of both histamine and peptidoleukotrienes from lung fragments. Piceatannol did not inhibit exogenous arachidonic acid-induced release of peptidoleukotrienes from lung fragments. Our data show for the first time that inhibition of Syk tyrosine kinase can attenuate anaphylactic bronchial contraction in vitro, probably via inhibition of mast cell degranulation.
Seow
Cherng-Jye
CJ
Department of Pharmacology, Faculty of Medicine, National University of Singapore, MD2 18 Medical Drive, Singapore 119260, Singapore.
Chue
Sung-Chian
SC
Wong
W S Fred
WS
D000402:Airway Obstruction / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013267:Stilbenes / Q000494:pharmacology*; D000072377:Syk Kinase
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D010047:Ovalbumin; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase