Oh-ishi S, Hayashi I, Yamaki K, Utsunomiya I
Department of Pharmacology, School of Pharmac. Sci., Kitasato Univ., Tokyo, Japan.
Agents Actions Suppl. 1992;38 ( Pt 1):277-91. doi: 10.1007/978-3-0348-7321-5_36.
The Brown Norway Katholiek (B/N-Ka) strain rat is the only animal strain that demonstrates deficiency in plasma HMW- and LMW-kininogens with a low level of prekallikrein. We developed an RIA for rat HMW-kininogen, LMW-kininogen, and T-kininogen, and using them measured these proteins in B/N-Ka and normal strain (B/N-Ki) rats. Plasma level of immunoreactive as well as kinin-releasing HMW-kininogen and LMW-kininogen in B/N-Ka rats was either around 3% of their levels in the normal B/N-Ki rats. The cause of the plasma deficiency of kininogens in the B/N-Ka strain was examined by 35S-methionine uptake of primary cultures of hepatocytes from the B/N-Ki and B/N-Ka strains. The results indicated that the kininogens were synthesized in the B/N-Ka liver but not secreted into the medium. Northern blot analysis of poly A(+)RNA extracted from the livers of both strains demonstrated that the band corresponding to mRNA of HMW-kininogen was present in the mRNA from B/N-Ka liver as well as in that from the B/N-Ki one. The band was similar in size and intensity in both cases. This result confirmed the data that immunoreactive HMW-kininogen was found in the liver of B/N-Ka rats (12). Thus, the cause of plasma deficiency of HMW-kininogen in the mutant appears to be secretory defect in nature. The B/N-Ka rats showed less reactivity to the inflammatory stimulus, such as carrageenin or kaolin, but the strain expressed almost the same response as normal rats to phorbol ester (PMA) or zymosan for pleurisy induction. These results indicate that kinin may play an important role in exudation in carrageenin- and kaolin-induced edema but not in that induced by PMA or zymosan. The deficient rat strain could be useful for differentiation of the inflammatory model which shows involvement of the kinin system.
棕色挪威天主教（B/N-Ka）品系大鼠是唯一一种血浆高分子量和低分子量激肽原缺乏且前激肽释放酶水平较低的动物品系。我们开发了一种用于大鼠高分子量激肽原、低分子量激肽原和T-激肽原的放射免疫分析法，并使用它们来检测B/N-Ka和正常品系（B/N-Ki）大鼠中的这些蛋白质。B/N-Ka大鼠血浆中免疫反应性以及释放激肽的高分子量激肽原和低分子量激肽原的水平约为正常B/N-Ki大鼠的3%。通过对B/N-Ki和B/N-Ka品系肝细胞原代培养物进行35S-甲硫氨酸摄取，研究了B/N-Ka品系血浆中激肽原缺乏的原因。结果表明，激肽原在B/N-Ka肝脏中合成，但未分泌到培养基中。对从两个品系肝脏中提取的多聚A(+)RNA进行Northern印迹分析表明，与高分子量激肽原mRNA相对应的条带在B/N-Ka肝脏的mRNA以及B/N-Ki肝脏的mRNA中均存在。两种情况下条带的大小和强度相似。这一结果证实了在B/N-Ka大鼠肝脏中发现免疫反应性高分子量激肽原的数据（12）。因此，该突变体中高分子量激肽原血浆缺乏的原因似乎本质上是分泌缺陷。B/N-Ka大鼠对角叉菜胶或高岭土等炎症刺激的反应较小，但该品系对佛波酯（PMA）或酵母聚糖诱导胸膜炎的反应与正常大鼠几乎相同。这些结果表明，激肽可能在角叉菜胶和高岭土诱导的水肿渗出中起重要作用，但在PMA或酵母聚糖诱导的水肿中不起作用。这种激肽原缺乏的大鼠品系可能有助于区分涉及激肽系统的炎症模型。
