Chen L M, Ma J x, Liang Y M, Chao L, Chao J
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
J Biol Chem. 1996 Nov 1;271(44):27590-4. doi: 10.1074/jbc.271.44.27590.
The kallikrein-kinin system participates in blood pressure regulation. One of the kallikrein-kinin system components, kallikrein-binding protein, binds to tissue kallikrein and inhibits its activity in vitro. To investigate potential roles of rat kallikrein-binding protein (RKBP) in vivo, we have developed transgenic mice that express an RKBP gene under the control of the mouse metallothionein metal-responsive promoter. Expression of the transgene, RKBP, was detected in the liver, kidney, lung, heart, pancreas, salivary glands, spleen, brain, testis, and adrenal gland at the mRNA and protein levels. Systolic blood pressures of homozygous transgenic mice were 88.5 +/- 0.8 mm Hg (mean +/- S.E., n = 19, P < 0.001) for one line and 88.8 +/- 1.6 mm Hg (mean +/- S.E., n = 19, P < 0.001) for another, as compared with 100.5 +/- 0.8 mm Hg (mean +/- S.E., n = 18) for control mice. Direct blood pressure measurements of these transgenic mice through an arterial cannula showed similar reductions of blood pressure. Intravenous injection of purified RKBP into mice via a catheter produced a dose-dependent reduction of the mean arterial blood pressure. Our findings suggest that RKBP may function as a vasodilator in vivo, independent of regulating the activity of tissue kallikrein.
激肽释放酶 - 激肽系统参与血压调节。激肽释放酶 - 激肽系统的成分之一，激肽释放酶结合蛋白，在体外与组织激肽释放酶结合并抑制其活性。为了研究大鼠激肽释放酶结合蛋白（RKBP）在体内的潜在作用，我们构建了在小鼠金属硫蛋白金属反应性启动子控制下表达RKBP基因的转基因小鼠。在mRNA和蛋白质水平上，在肝脏、肾脏、肺、心脏、胰腺、唾液腺、脾脏、大脑、睾丸和肾上腺中检测到转基因RKBP的表达。一条纯合转基因小鼠品系的收缩压为88.5±0.8 mmHg（平均值±标准误，n = 19，P <0.001），另一条为88.8±1.6 mmHg（平均值±标准误，n = 19，P <0.001），而对照小鼠的收缩压为100.5±0.8 mmHg（平均值±标准误，n = 18）。通过动脉插管对这些转基因小鼠进行直接血压测量显示血压有类似程度的降低。通过导管将纯化的RKBP静脉注射到小鼠体内会使平均动脉血压产生剂量依赖性降低。我们的研究结果表明，RKBP在体内可能作为一种血管舒张剂发挥作用，与调节组织激肽释放酶的活性无关。
