Baumgartner Heidi K, Kirbiyik Uzay, Coskun Tamer, Chu Shaoyou, Montrose Marshall H
Indiana University School of Medicine, Department of Cellular and Integrative Physiology, Indianapolis 46202, USA.
J Physiol. 2002 Nov 1;544(3):871-82. doi: 10.1113/jphysiol.2002.024620.
In the stomach, production of prostaglandins by cyclo-oxygenase (COX) is believed to be important in mucosal defence. We tested the hypothesis that endogenous COX activity is required for protective gastric surface pH control. Intact stomachs of anaesthetized mice were perfused with a weakly buffered solution (150 mM NaCl + 4 mM Homopipes) at pH values from 2.5 to 7.0. Gastric effluents were collected to measure pH and estimate amounts of acid or alkali secretion in nanomoles secreted per minute. A switch from net acid to net alkali secretion was seen in response to acidifying luminal pH with an apparent 'set point' between pH 4 and 5. At luminal pH 3, the net alkali secretion (12.7 +/- 2.8 nmol OH(-) equivalents min(-1)) was abolished (2.2 +/- 1.7 nmol OH(-) min(-1)) by the non-specific COX inhibitor indomethacin (5 mg kg(-1) I.P.). Similar inhibition was observed using a COX-1 inhibitor (SC-560; 10 mg kg(-1) I.P.), but not a COX-2 inhibitor (NS-398; 10 mg kg(-1) I.P.). Subsequent treatment with 16,16-dimethyl prostaglandin E(2) (dm-PGE(2); 1 mg kg(-1) I.P.) rescued the alkali secretion (21.8 +/- 2.7 nmol OH(-) min(-1)). In either the absence or presence of the H(+),K(+)-ATPase inhibitor omeprazole (60 mg kg(-1) I.P.), indomethacin blocked similar amounts of net alkali secretion (10.5 +/- 2.7 and 16.4 +/- 3.4 nmol OH(-) min(-1), respectively). We also used in vivo confocal microscopy to examine pH near the mucosal surface. The gastric mucosal surface of anaesthetized mice was exposed and mucosal surface pH was imaged using the fluorescence intensity ratio of Cl-NERF as a pH indicator. Results showed a switch from a continuous net acid to net alkali secretion by the stomach in response to changing superfusate pH from 5 to 3. At luminal pH 3, the relatively alkaline surface pH (4.3 +/- 0.1) was acidified (3.6 +/- 0.2) by indomethacin, and subsequent dm-PGE(2) restored surface pH (4.2 +/- 0.2). We conclude that the pre-epithelial alkaline layer is regulated by endogenous COX activity.
在胃中，环氧化酶（COX）产生前列腺素被认为在黏膜防御中起重要作用。我们测试了内源性COX活性是保护性胃表面pH值控制所必需的这一假设。用pH值为2.5至7.0的弱缓冲溶液（150 mM氯化钠 + 4 mM高哌嗪）灌注麻醉小鼠的完整胃。收集胃流出物以测量pH值，并估计每分钟分泌的酸或碱分泌量（以纳摩尔计）。随着腔内pH值酸化，观察到从净酸分泌到净碱分泌的转变，其表观“设定点”在pH 4至5之间。在腔内pH值为3时，非特异性COX抑制剂吲哚美辛（5 mg kg⁻¹腹腔注射）使净碱分泌（12.7 ± 2.8 nmol OH⁻当量min⁻¹）消失（2.2 ± 1.7 nmol OH⁻ min⁻¹）。使用COX - 1抑制剂（SC - 560；10 mg kg⁻¹腹腔注射）观察到类似的抑制作用，但使用COX - 2抑制剂（NS - 398；10 mg kg⁻¹腹腔注射）则未观察到。随后用16,16 - 二甲基前列腺素E₂（dm - PGE₂；1 mg kg⁻¹腹腔注射）处理可恢复碱分泌（21.8 ± 2.7 nmol OH⁻ min⁻¹）。在存在或不存在H⁺，K⁺ - ATP酶抑制剂奥美拉唑（60 mg kg⁻¹腹腔注射）的情况下，吲哚美辛阻断的净碱分泌量相似（分别为10.5 ± 2.7和16.4 ± 3.4 nmol OH⁻ min⁻¹）。我们还使用体内共聚焦显微镜检查黏膜表面附近的pH值。暴露麻醉小鼠的胃黏膜表面，并使用Cl - NERF的荧光强度比作为pH指示剂对黏膜表面pH值进行成像。结果显示，随着灌注液pH值从5变为3，胃从持续的净酸分泌转变为净碱分泌。在腔内pH值为3时，相对碱性的表面pH值（4.3 ± 0.1）被吲哚美辛酸化（3.6 ± 0.2），随后dm - PGE₂使表面pH值恢复（4.2 ± 0.2）。我们得出结论，上皮前碱性层受内源性COX活性调节。
