Kargman S, Charleson S, Cartwright M, Frank J, Riendeau D, Mancini J, Evans J, O'Neill G
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.
Gastroenterology. 1996 Aug;111(2):445-54. doi: 10.1053/gast.1996.v111.pm8690211.
BACKGROUND & AIMS: In the gastrointestinal tract, prostaglandins are implicated as important mediators of normal physiological processes. Prostaglandin G/H synthase (PGHS) is the first enzyme leading to the formation of prostaglandins. Two forms exist: the constitutive PGHS-1 and the inducible PGHS-2 isoforms. The purpose of this study was to examine the expression of PGHS-1 and -2 in gastrointestinal tissues.
PGHS-1 and -2 expression and activity were examined in rat, dog, monkey, and human gastrointestinal tracts by immunoblot and biochemical assays.
PGHS-1 but not PGHS-2 protein was identified in all gastrointestinal tissues. PGHS-1 protein varied throughout the gastrointestinal tracts; interspecies differences were also noted. Immunohistochemical studies showed PGHS-1 staining of rat endothelial cells in all gastrointestinal regions; PGHS-2-specific staining was noted in a subset of macrophages in 3 of 22 rats examined. Elevated activity was shown in tissues expressing greater concentrations of PGHS-1 protein. Indomethacin, a nonsteroidal anti-inflammatory drug that inhibits both isoforms, inhibited prostaglandin synthesis, whereas NS-398, a selective PGHS-2 inhibitor, showed little or no inhibition of prostaglandin synthesis in gastrointestinal tissues.
These results indicate that prostaglandins produced in normal gastrointestinal tissue and required for normal physiological functioning are derived from the PGHS-1 isoform.
在胃肠道中，前列腺素被认为是正常生理过程的重要介质。前列腺素G/H合酶（PGHS）是前列腺素形成过程中的首个酶。它有两种形式：组成型PGHS-1和诱导型PGHS-2同工型。本研究的目的是检测PGHS-1和-2在胃肠道组织中的表达。
通过免疫印迹和生化分析检测大鼠、犬、猴和人类胃肠道中PGHS-1和-2的表达及活性。
在所有胃肠道组织中均鉴定出PGHS-1蛋白，但未检测到PGHS-2蛋白。PGHS-1蛋白在整个胃肠道中有所不同；还注意到种间差异。免疫组织化学研究显示，在所有胃肠道区域大鼠内皮细胞均有PGHS-1染色；在22只接受检查的大鼠中的3只，部分巨噬细胞中有PGHS-2特异性染色。在表达更高浓度PGHS-1蛋白的组织中显示出活性升高。吲哚美辛是一种抑制两种同工型的非甾体抗炎药，可抑制前列腺素合成，而选择性PGHS-2抑制剂NS-398在胃肠道组织中对前列腺素合成几乎没有抑制作用。
这些结果表明，正常胃肠道组织中产生的、正常生理功能所需的前列腺素源自PGHS-1同工型。
