Hojvat S A, Musch M W, Miller R J
J Pharmacol Exp Ther. 1983 Sep;226(3):749-55.
When rabbit ileal mucosa was incubated with exogenous [3H]arachidonic acid (AA), its major metabolites, identified by comigration with known standards on thin-layer chromatography, were prostaglandin (PG) E2, 6-keto-PGF1 alpha and to a lesser extent PGF2 alpha and PGD2. The rate of prostanoid release from the serosal surface of the mucosa only was increased after incubation th either bradykinin, lys-bradykinin, melittin or the calcium ionophore A 23187, in a rapid and dose-dependent fashion. Peptide concentrations as low as 10(-9) M were effective. Kinin-induced release of AA or its metabolites required the presence of Ca++ in the incubation medium. Stimulation of prostanoid release by lys-bradykinin was completely blocked by indomethacin. The combined lipoxygenase/cyclooxygenase inhibitors BW 755 and eicosa-5,8,11,14-tetraynoic acid and the lipoxygenase inhibitor nordihydroguaiaretic acid also blocked the stimulation of PG synthesis by lys-bradykinin. These inhibitors caused an increase in levels of AA released from the tissue by lys-bradykinin. The phospholipase inhibitors, mepacrine and U- 10029, inhibited the lys-bradykinin-stimulated release of both prostanoids and AA. At higher concentrations, U- 10029 inhibited the stimulation of transepithelial potential difference and short-circuit current across rabbit ileal mucosa produced by lys-bradykinin. These results support the hypothesis that bradykinin-stimulated intestinal secretion may be mediated by PGs.
当兔回肠黏膜与外源性[3H]花生四烯酸（AA）一起孵育时，通过在薄层色谱上与已知标准品共迁移鉴定出的其主要代谢产物为前列腺素（PG）E2、6-酮-PGF1α，以及含量较少的PGF2α和PGD2。仅在黏膜浆膜表面的类前列腺素释放速率，在与缓激肽、赖氨酰缓激肽、蜂毒肽或钙离子载体A 23187孵育后，以快速且剂量依赖性的方式增加。低至10(-9) M的肽浓度即有效。激肽诱导的AA或其代谢产物释放需要孵育培养基中存在Ca++。赖氨酰缓激肽对类前列腺素释放的刺激被吲哚美辛完全阻断。脂氧合酶/环氧化酶联合抑制剂BW 755和5,8,11,14-二十碳四烯酸以及脂氧合酶抑制剂去甲二氢愈创木酸也阻断了赖氨酰缓激肽对PG合成的刺激。这些抑制剂导致赖氨酰缓激肽从组织中释放的AA水平升高。磷脂酶抑制剂米帕林和U-10029抑制了赖氨酰缓激肽刺激的类前列腺素和AA释放。在较高浓度下，U-10029抑制了赖氨酰缓激肽引起的兔回肠黏膜跨上皮电位差和短路电流的刺激。这些结果支持缓激肽刺激的肠道分泌可能由PG介导的假说。
