Seow Cherng-Jye, Chue Sung-Chian, Wong W S Fred
Department of Pharmacology, Faculty of Medicine, National University of Singapore, MD2 18 Medical Drive, Singapore 119260, Singapore.
Eur J Pharmacol. 2002 May 17;443(1-3):189-96. doi: 10.1016/s0014-2999(02)01534-0.
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.
已证明，非跨膜蛋白酪氨酸激酶（如Lyn和Syk）的激活是肥大细胞上Fc受体（FcεRI）交联后最早可检测到的信号反应，会导致肥大细胞脱颗粒。本研究检测了Syk选择性酪氨酸激酶抑制剂白皮杉醇（3,4,3',5'-四羟基反式芪，10 - 100微摩尔）对卵清蛋白诱导的离体豚鼠支气管过敏性收缩以及切碎肺组织中组胺和肽白三烯释放的影响。用白皮杉醇预处理可轻微抑制卵清蛋白诱导的过敏性支气管收缩峰值，但能显著（P<0.05）促进过敏性收缩支气管的舒张。白皮杉醇不抑制组胺、白三烯D4或氯化钾直接诱导的支气管收缩，也不能逆转现有的过敏性支气管收缩。30微摩尔及以上浓度的白皮杉醇能显著（P<0.05）抑制卵清蛋白诱导的肺组织碎片中组胺和肽白三烯的释放。白皮杉醇不抑制外源性花生四烯酸诱导的肺组织碎片中肽白三烯的释放。我们的数据首次表明，抑制Syk酪氨酸激酶可能通过抑制肥大细胞脱颗粒来减轻体外过敏性支气管收缩。
