Inhibition of ACh-stimulated exocytosis by NSAIDs in guinea pig antral mucous cells: autocrine regulation of mucin secretion by PGE2.
Inhibition of ACh-stimulated exocytosis by NSAIDs in guinea pig antral mucous cells: autocrine regulation of mucin secretion by PGE2.
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DOI：
10.1152/ajpgi.00060.2004
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
C. Shimamoto;S. Fujiwara;Masumi Kato;S. Ito;K. Katsu;H. Mori;T. Nakahari
中科院分区：
文献类型：
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作者：
C. Shimamoto;S. Fujiwara;Masumi Kato;S. Ito;K. Katsu;H. Mori;T. Nakahari
用视频光学显微镜观察了吲哚美辛（IDM）和阿司匹林（阿萨）对乙酰胆碱（ACh）（10 μ M）刺激的豚鼠胃窦粘膜细胞胞吐事件的影响。IDM或阿萨抑制环氧合酶（考克斯），分别使ACh刺激的胞吐事件频率降低30%或60%。当加入IDM或考克斯的底物花生四烯酸（AA）时，阿萨诱导的抑制程度（60%）降低30%。IDM，不像阿萨，似乎诱导AA的积累，这提高了频率的乙酰胆碱刺激ASA处理的细胞中的胞吐事件。ONO-8713（100 μ M; EP 1-EP 4前列腺素受体的抑制剂）和N-[2-（（对溴肉桂基）氨基）乙基]-5-异喹啉磺酰胺，HCl（H-89，20 μ M; PKA的抑制剂）也使乙酰胆碱刺激的胞吐事件的频率降低60%。然而，补充PGE（2）（1 μ M）阻止IDM诱导的乙酰胆碱刺激的胞吐事件频率的降低。SC-560（一种考克斯-1抑制剂）可使ACh刺激的胞吐事件频率降低30%，但NS-398（一种考克斯-2抑制剂）则无此作用。此外，IDM降低了由离子霉素刺激的胞吐事件的频率，表明考克斯-1活性是由细胞内Ca（2+）浓度（[Ca（2+）]（i））的增加刺激的。ACh和离子霉素增加胃窦粘膜细胞PGE（2）的释放。总之，在ACh刺激的胃窦粘液细胞中，[Ca（2+）]（i）的增加激活了Ca（2+）调节的胞吐事件和由考克斯-1介导的PGE（2）释放。释放的PGE（2）诱导cAMP的积累，这增强了Ca（2+）调节的胞吐作用。PGE（2）介导的自分泌机制维持ACh刺激时胃窦粘液细胞高水平的粘蛋白释放。
The effects of indomethacin (IDM) and aspirin (ASA) on ACh (10 microM) -stimulated exocytotic events were studied in guinea pig antral mucous cells by using video optical microscopy. IDM or ASA, which inhibits cyclooxygenase (COX), decreased the frequency of ACh-stimulated exocytotic events by 30% or 60%, respectively. The extent of inhibition induced by ASA (60%) decreased by 30% when IDM or arachidonic acid (AA, the substrate of COX) was added. IDM, unlike ASA, appears to induce the accumulation of AA, which enhances the frequency of ACh-stimulated exocytotic events in ASA-treated cells. ONO-8713 (100 microM; an inhibitor of the EP1-EP4 prostaglandin receptors) and N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, HCl (H-89, 20 microM; an inhibitor of PKA) also decreased the frequency of ACh-stimulated exocytotic events by 60%. However, the supplementation of PGE(2) (1 microM) prevented the IDM-induced decrease in the frequency of ACh-stimulated exocytotic events. SC-560 (an inhibitor of COX-1) decreased the frequency of ACh-stimulated exocytotic events by 30%, but NS-398 (an inhibitor of COX-2) did not. Moreover, IDM decreased the frequency of exocytotic events stimulated by ionomycin, suggesting that COX-1 activity is stimulated by an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)). ACh and ionomycin increased PGE(2) release in antral mucosal cells. In conclusion, in ACh-stimulated antral mucous cells, an increase in [Ca(2+)](i) activates Ca(2+)-regulated exocytotic events and PGE(2) release mediated by COX-1. The released PGE(2) induces the accumulation of cAMP, which enhances the Ca(2+)-regulated exocytosis. The autocrine mechanism mediated by PGE(2) maintains the high-level mucin release from antral mucous cells during ACh stimulation.