Bradykinin- and substance P-induced edema formation in the hamster cheek pouch is tyrosine kinase dependent.
Bradykinin- and substance P-induced edema formation in the hamster cheek pouch is tyrosine kinase dependent.
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缓激肽和 P 物质诱导的仓鼠颊囊水肿形成依赖于酪氨酸激酶。
DOI：
10.1152/japplphysiol.00941.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Rubinstein,Israel
中科院分区：
文献类型：
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作者：
Rubinstein,Israel
本研究的目的是确定蛋白酪氨酸激酶(一种普遍存在的调节内皮细胞功能的细胞内信号酶家族)是否调节缓激肽和P物质诱导的完整仓鼠颊囊微循环大分子外流增加。在活体显微镜下，我发现将缓激肽或P物质(分别为0.5kDa和1.0kDa M)注入颊囊可引起显著的、浓度依赖的渗漏部位的形成，并增加荧光素异硫氰酸酯-葡聚糖(μ-葡聚糖；分子质量，70 kDa；P<；0.05)的清除。金雀异黄素(1μM)或酪氨酸蛋白25(10μM)这两种结构无关、非特异性蛋白酪氨酸激酶抑制剂(P<；0.0 5)可显著减弱上述反应。可以想象，参与这一过程的激酶(S)可能是激动剂专一性的，因为染料木素在减弱缓激肽诱导的反应方面比酪氨酸蛋白25更有效，而P物质则相反。两种抑制剂对腺苷(0.5M)诱导的反应没有显著影响(P>；0.5)。综上所述，这些数据表明，蛋白酪氨酸激酶代谢途径以一种特定的方式部分调节缓激肽和P物质在完整的仓鼠颊囊微循环中的水肿性效应。
The purpose of this study was to determine whether protein tyrosine kinase, a ubiquitous family of intracellular signaling enzymes that regulates endothelial cell function, modulates bradykinin- and substance P-induced increase in macromolecular efflux from the intact hamster cheek pouch microcirculation. Using intravital microscopy, I found that suffusion of bradykinin or substance P (each, 0.5 and 1.0 μM) onto the cheek pouch elicited significant, concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (FITC-dextran; molecular mass, 70 kDa;P< 0.05). These responses were significantly attenuated by suffusion of genistein (1.0 μM) or tyrphostin 25 (10 μM), two structurally unrelated, nonspecific protein tyrosine kinase inhibitors (P< 0.05). Conceivably, the kinase(s) involved in this process could be agonist specific because genistein was more effective than tyrphostin 25 in attenuating bradykinin-induced responses while the opposite was observed with substance P. Both inhibitors had no significant effects on adenosine (0.5 M)-induced responses (P> 0.5). Collectively, these data suggest that the protein tyrosine kinase metabolic pathway modulates, in part, the edemagenic effects of bradykinin and substance P in the intact hamster cheek pouch microcirculation in a specific fashion.