Ljunggren O, Vavrek R, Stewart J M, Lerner U H
Department of Oral Pathology, University of Umeå, Sweden.
J Bone Miner Res. 1991 Aug;6(8):807-15. doi: 10.1002/jbmr.5650060805.
The receptor subtype mediating the bradykinin (Bk)-induced burst of prostaglandin formation in osteoblasts has been studied. Bk, but not des-Arg9-Bk, induced the formation of prostaglandin E2 and prostacyclin in neonatal mouse calvarial bones incubated for 30 minutes. Bk-induced prostaglandin synthesis is neonatal mouse calvarial bones was significantly inhibited by the B2 Bk receptor antagonist D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk. The B2 Bk receptor agonists Bk and Lys-Bk, but not the B1 Bk receptor agonist des-Arg9-Bk, caused a rapid burst (5 minutes) of prostaglandin E2 and prostacyclin formation in isolated osteoblast-like cells from neonatal mouse calvarial bones and in the murine osteoblastic cell lineage MC3T3-E1. When comparing the relative potency of different kinin analogs on their stimulatory effect on prostaglandin formation in isolated osteoblast-like cells and in MC3T3-E1 cells, we found that Bk = Lys-Bk greater than Met-lys-Bk much much greater than Des-Arg9-Bk. Bk-induced prostaglandin synthesis in isolated osteoblast-like cells and in MC3T3-E1 cells was inhibited by D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk, whereas the B1 Bk receptor antagonist des-Arg9-Leu8-Bk had no effect. Total binding of 3H-Bk (3-20 nM; 4 degrees C) to whole MC3T3-E1 cells reached a maximum after 4-5 h. An excess of nonradioactive Bk (1 microM) reduced cell-associated radioactivity by 20-30%. The B2 Bk receptor agonist Bk and the B2 Bk receptor antagonist D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk were able to reduce specific binding, but the B1 Bk receptor agonist des-Arg9-Bk was unable to reduce the specific binding of 3H-Bk to whole MC3T3-E1 cells. These findings indicate the presence of B2 Bk receptors on osteoblasts coupled to enhanced prostaglandin synthesis.
研究了介导缓激肽（Bk）诱导成骨细胞中前列腺素生成爆发的受体亚型。Bk而非去精氨酸9-缓激肽（des-Arg9-Bk）可诱导新生小鼠颅骨在孵育30分钟后生成前列腺素E2和前列环素。Bk诱导的新生小鼠颅骨中前列腺素合成受到B2缓激肽受体拮抗剂D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk的显著抑制。B2缓激肽受体激动剂Bk和赖氨酸-缓激肽（Lys-Bk），而非B1缓激肽受体激动剂去精氨酸9-缓激肽，可在来自新生小鼠颅骨的分离成骨样细胞和小鼠成骨细胞系MC3T3-E1中引发前列腺素E2和前列环素生成的快速爆发（5分钟）。比较不同激肽类似物对分离的成骨样细胞和MC3T3-E1细胞中前列腺素生成的刺激作用的相对效力时，我们发现Bk = Lys-Bk大于甲硫氨酸-赖氨酸-缓激肽（Met-lys-Bk）远大于去精氨酸9-缓激肽。D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk抑制了分离的成骨样细胞和MC3T3-E1细胞中Bk诱导的前列腺素合成，而B1缓激肽受体拮抗剂去精氨酸9-亮氨酸8-缓激肽（des-Arg9-Leu8-Bk）则无作用。3H-Bk（3 - 20 nM；4℃）与整个MC3T3-E1细胞的总结合在4 - 5小时后达到最大值。过量的非放射性Bk（1μM）使细胞相关放射性降低了20 - 30%。B2缓激肽受体激动剂Bk和B2缓激肽受体拮抗剂D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk能够降低特异性结合，但B1缓激肽受体激动剂去精氨酸9-缓激肽无法降低3H-Bk与整个MC3T3-E1细胞的特异性结合。这些发现表明成骨细胞上存在与增强的前列腺素合成相关联的B2缓激肽受体。
