Pandol S J, Hsu Y L, Kondratenko N F, Schoeffield-Payne M S, Steinbach J H
Department of Medicine, Veterans Administration Medical Center, San Diego, California.
Am J Physiol. 1991 Mar;260(3 Pt 1):G423-33. doi: 10.1152/ajpgi.1991.260.3.G423.
The present experiments were performed to determine pathways responsible for arachidonic acid release stimulated by cholecystokinin (CCK) and phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA), and the roles of pathways in the secretory response in dispersed acini from guinea pig pancreas. Both CCK-octapeptide (CCK-OP) and PMA increased intracellular arachidonic acid. To determine the source of released arachidonic acid, we measured the effects of PMA and CCK-OP on cellular 1,2-diacylglycerol and lysophosphatidylcholine (LPC) and of diglyceride lipase inhibitor RHC 80267 on [3H]arachidonic acid release. Both PMA and CCK-OP increased 1,2-diacylglycerol and LPC. RHC 80267 had no effect on LPC but inhibited the increase in [3H]arachidonic acid release with a concentration of CCK-OP that was maximal for enzyme secretion. The increase in [3H]arachidonic acid release with PMA or a supramaximal concentration of CCK-OP was not inhibited by RHC 80267. In parallel fashion, RHC 80267 inhibited amylase release caused by maximally effective concentrations of CCK-OP but not that caused by PMA or by supramaximally effective concentrations of CCK-OP. Arachidonic acid stimulated amylase release. Exogenous addition of phospholipase A2 caused increases in [3H]arachidonic acid release, LPC formation, and amylase release. The results indicate that there are at least two pathways responsible for the increase in free cellular arachidonic acid stimulated by pancreatic agonists. One is sequential action of phospholipase C and diglyceride lipase on phosphatidylinositol. The other is a phospholipase A action on phosphatidylcholine. The results also suggest a stimulatory role for both pathways in the secretory response.
进行本实验以确定负责胆囊收缩素（CCK）和佛波酯4β-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）刺激的花生四烯酸释放的途径，以及这些途径在豚鼠胰腺分散腺泡分泌反应中的作用。CCK八肽（CCK-OP）和PMA均增加细胞内花生四烯酸。为了确定释放的花生四烯酸的来源，我们测量了PMA和CCK-OP对细胞1,2-二酰基甘油和溶血磷脂酰胆碱（LPC）的影响，以及甘油二酯脂肪酶抑制剂RHC 80267对[3H]花生四烯酸释放的影响。PMA和CCK-OP均增加1,2-二酰基甘油和LPC。RHC 80267对LPC无影响，但抑制了[3H]花生四烯酸释放的增加，该浓度的CCK-OP对酶分泌具有最大作用。RHC 80267不抑制PMA或超最大浓度CCK-OP引起的[3H]花生四烯酸释放增加。以平行方式，RHC 80267抑制由最大有效浓度的CCK-OP引起的淀粉酶释放，但不抑制由PMA或超最大有效浓度的CCK-OP引起的淀粉酶释放。花生四烯酸刺激淀粉酶释放。外源性添加磷脂酶A2导致[3H]花生四烯酸释放、LPC形成和淀粉酶释放增加。结果表明，至少有两条途径负责胰腺激动剂刺激的游离细胞花生四烯酸增加。一条是磷脂酶C和甘油二酯脂肪酶对磷脂酰肌醇的顺序作用。另一条是磷脂酶A对磷脂酰胆碱的作用。结果还表明这两条途径在分泌反应中均具有刺激作用。
