Kallikrein stimulates arachidonic acid release and production of prostaglandins from TEA3A1 endocrine thymic epithelial cells.
Kallikrein stimulates arachidonic acid release and production of prostaglandins from TEA3A1 endocrine thymic epithelial cells.
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激肽释放酶刺激 TEA3A1 内分泌胸腺上皮细胞释放花生四烯酸和产生前列腺素。
DOI：
10.1042/bj2580351
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Hayashi,J
中科院分区：
文献类型：
--
作者：
Sun,L;Piltch,A;Hayashi,J
利用TEA3A1大鼠胸腺内分泌上皮细胞，我们证明激肽释放酶(EC 3.4.21.35)不仅能刺激TEA3A1细胞释放花生四烯酸(AA)及其代谢产物，而且还能促进细胞内前列腺素E_2(PGE_2)和血栓素B_2(TXB_2)的合成。2折。激肽释放酶的刺激作用具有剂量和时间依赖性，并可被激肽释放酶抑制剂抑肽酶阻断。发现磷脂酶A抑制剂OnoRS082[2-(对戊基肉桂酰基)氨基-4-氯苯甲酸]和MEPACRINE(6-chloro-9-[(4-dimethylamino)-1-methyl)]amino-2-methoxyacridine；Qinacine也能抑制激肽释放酶刺激的AA及其代谢产物的释放。提示激肽释放酶的兴奋作用可能是通过磷脂酶A2途径实现的。研究了缓激肽的作用，即使在高剂量(10微克/毫升)也没有明显的刺激作用。这表明激动素的形成在激肽释放酶刺激TEA3A1细胞释放AA的过程中没有作用。此外，通过加入已知的肾素、胃酶和组织蛋白酶D的抑制剂胃抑素A，激肽释放酶的作用也被完全消除，组织蛋白酶D本身不抑制激肽释放酶。这表明激肽释放酶不是直接作用于磷脂酶样酶。至少还有一种酶，一种胃抑素A可抑制的蛋白酶，在激肽释放酶诱导的AA释放调节中起到中介作用。
Using TEA3A1 rat endocrine thymic epithelial cells, we demonstrated that kallikrein (EC 3.4.21.35) not only stimulated the release of arachidonic acid (AA) and its metabolites from TEA3A1 cells but also enhanced the intracellular synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) by approx. 2-fold. The stimulatory effect of kallikrein was dose- and time-dependent and could be blocked by aprotinin, a kallikrein inhibitor. It was found that the phospholipase A inhibitors ONO RS082 [2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid], and mepacrine (6-chloro-9-[(4-dimethylamino)-1-methyl)]amino-2-methoxyacridine; quinacrine) also inhibited the kallikrein-stimulated release of AA and its metabolites. It is suggested that the kallikrein-induced stimulatory effect might be mediated through a phospholipase A2 pathway. The effect of bradykinin was studied and no significant stimulation was observed, even at a high dose (10 micrograms/ml). This suggested that the formation of kinin does not have a role in the kallikrein-induced stimulation of AA release from TEA3A1 cells. Furthermore, the effect of kallikrein was also totally abolished by adding pepstatin A, a known inhibitor of renin, pepsin and cathepsin D which does not inhibit kallikrein itself. This indicates that kallikrein did not act on the phospholipase-like enzyme directly. There is at least one more enzyme, a pepstatin A-inhibitable proteinase, that acts as a mediator for kallikrein-induced regulation of AA release.